• It is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. (antibodyguide.com)
  • HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. (wikipedia.org)
  • ErbB-2 was named for its similarity to ErbB (avian erythroblastosis oncogene B), the oncogene later found to code for EGFR. (wikipedia.org)
  • The molecular mechanism underlying its development is complex, but its carcinogenesis has been proposed to occur with cell proliferation and resistance to apoptosis, driven by the signaling activity of abundant EGFR and receptor tyrosine-protein kinase erbB-2. (bvsalud.org)
  • In the present study, T24 bladder cancer cell lines with EGFR-overexpression were constructed, before the multi-target inhibitor CUDC-101 was used to investigate its potential as a targeted therapeutic agent for bladder cancer using chemosensitivity methods. (bvsalud.org)
  • It has been proposed that oncogenes (EGFR (ERBB), MET) and tumor suppressors (PTEN, TP53) may also be capable of altering the vesicular release of tissue factor (TF) from cells [4-6]. (biomedres.us)
  • Neratinib is an investigational, orally administered, irreversible inhibitor of the ErbB1 (EGFR), ErbB2 (HER2) and ErbB4 (HER4) kinases. (her2support.org)
  • EGFR (Epidermal growth factor receptor, HER1, ErbB1) is encoded by the EGFR gene located on chromosome 7 in humans. (thermofisher.com)
  • EGFR belongs to the HER/ERbB family of proteins that includes three other receptor tyrosine kinases, ERbB2, ERbB3, ERbB4. (thermofisher.com)
  • EGFR is a transmembrane receptor and binding of its cognate ligands such as EGF (Epidermal Growth Factor) and TGF alpha (Transforming Growth Factor alpha) to the extracellular domain leads to EGFR dimerization followed by autophosphorylation of the tyrosine residues in the cytoplasmic domain. (thermofisher.com)
  • Phosphorylation of EGFR at certain residues is also mediated by Src-non-receptor kinase. (thermofisher.com)
  • Phosphorylation of EGFR at Y1086 specifically allows binding of the adaptor protein GRB2, leading to activation of the MAPK pathway. (thermofisher.com)
  • Upon receptor activation and signaling, EGFR is endocytosed and targeted for degradation or recycling. (thermofisher.com)
  • Mutations in the EGFR gene are associated with lung cancer and multiple alternatively spliced transcript variants encode different protein isoforms of EGFR have been found. (thermofisher.com)
  • In our prior research of epidermal development aspect receptor (EGFR) dimerization dynamics at a single-molecule level, we demonstrated that receptor activation by ligand binding is certainly spatially asymmetric on cells overexpressing EGFR (ref. 13). (president2010.info)
  • Breast cancer therapy has improved following the development of drugs with specific molecular targets, exemplified by inhibitors of human epidermal growth factor receptor-2 (HER2) or epidermal growth factor receptor (EGFR) such as trastuzumab and lapatinib. (jcancer.org)
  • The ErbB-2 proto-oncogene, also called Neu, EGFR-2 or HER-2, is a member of the transmembrane receptor tyrosine kinase family, which also includes EGF receptor and EGFR-3 (HER-3 or ErbB-3). (activemotif.com)
  • It is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/c-neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). (rockland.com)
  • Mutations that lead to EGFR overexpression (known as upregulation) or overactivity have been associated with a number of cancers, including lung cancer and glioblastoma multiforme. (rockland.com)
  • EGFR (epidermal growth factor receptor) is a transmembrane protein and receptor for members of the epidermal growth factor (EGF) family of extracellular protein ligands. (promab.com)
  • Defective signaling of EGFR and other receptor tyrosine kinases in humans has been linked to diseases such as Alzheimer's disease, while overexpression has been linked to the development of various tumors. (promab.com)
  • Disruption of EGFR signaling by blocking the EGFR-binding site on the extracellular domain of the receptor or inhibiting intracellular tyrosine kinase activity prevents the growth of EGFR-expressing tumors and improves patient outcomes. (promab.com)
  • The anti-EGFR CAR in this product is approximately 56 kD and consists of anti-EGFR scFv (single-chain variable fragment) linked to a second-generation CAR (chimeric antigen receptor) containing the CD8 hinge and transmembrane domain and 4-1BB and CD3ζ signaling domains. (promab.com)
  • c- erb B-2 (HER-2/ neu ) is a 185 kDa receptor tyrosine kinase belonging to the epidermal growth factor receptor family, which also includes EGFR (HER-1), c- erb B-3 (HER-3), and c- erb B-4 (HER-4). (ihcworld.com)
  • The ErbB/HER family of receptor tyrosine kinases (RTKs) consists of four family members: the epidermal growth factor receptor (EGFR/ErbB1), HER2 (ErbB2/Neu), HER3 (ErbB3), and HER4 (ErbB4). (plos.org)
  • This family, which includes epidermal growth factor receptor (EGFR), plays a pivotal role in normal cell growth, lineage determination, repair, and functional differentiation. (medscape.com)
  • Selective compounds have been developed that target either the extracellular ligand-binding region of the EGFR (including a number of monoclonal antibodies [MAbs], immunotoxins, and ligand-binding cytotoxic agents) or the intracellular tyrosine kinase region (including various small-molecule inhibitors). (medscape.com)
  • The epidermal growth factor receptor (EGFR) continues to be implicated in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. (ecolowood.com)
  • The HER Alosetron family is comprised of four unique receptors: EGFR (also known as HER1 or ErbB-1) HER2 (ErbB-2 Neu) HER3 (ErbB-3) and HER4 (ErbB-4). (ecolowood.com)
  • The EGFR is definitely a 170-kd protein encoded by a 110-kb-long gene localized in the short arm of chromosome 7. (ecolowood.com)
  • They may be created as transmembrane precursors and could become subdivided into three organizations according with their affinity for just one or even more HER receptors: the 1st group includes ligands that bind specifically to EGFR (e.g. (ecolowood.com)
  • Three major intracellular signaling pathways linked to EGFR activation have been identified: the Ras-Raf-mitogen-activated protein (MAP) kinase pathway the phosphatidylinositol 3-kinase (PI-3 K)/Akt pathway and the Janus-kinase/signal transducer and activator of transcription (Jak2/STAT3) pathway. (ecolowood.com)
  • Once activated these pathways contribute to the development of a malignant cellular phenotype including resistance to apoptosis increased proliferation invasion metastasis and stimulation of angiogenesis (Figure 1).1 Figure 1 Epidermal growth factor receptor (EGFR) pathway activation during HNSCC carcinogenic process. (ecolowood.com)
  • Loss of heterozigosity (LOH) EGFR overexpression/amplification and cyclooxygenase-2 (COX2) dysregulation in pre-malignant lesions have been associated with … The EGFR has been implicated in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. (ecolowood.com)
  • The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. (bmj.com)
  • Alterations in receptor tyrosine kinases (TKs), such as the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1, include overexpression, amplification or mutations. (bmj.com)
  • 3 The development of molecular targeted therapies aimed at these molecular alterations has generated great optimism for the treatment of cancers such as NSCLC, and drugs targeting the EGFR tyrosine kinase domain are now available. (bmj.com)
  • The epidermal growth factor receptor (EGFR) is among the most well-studied signaling pathways in cancer progression. (bio-biz-navi.com)
  • Introduction Epidermal development element receptor (EGFR) was the 1st discovered from the ErbB category of receptor tyrosine kinases with a total of four users: Erbb1/EGFR, ErbB2/Her2, ErbB3 and ErbB4. (bio-biz-navi.com)
  • 2 Since its finding, EGFR continues to be characterized like a mediator of a multitude of signal transduction occasions that control cell proliferation, migration and success. (bio-biz-navi.com)
  • Overexpression of EGFR transforms NIH3T3 fibroblasts within an EGF-dependent way. (bio-biz-navi.com)
  • Improved EGFR proteins and transcript amounts correlate with poor prognosis in a variety of epithelial cancers, such as for example colorectal malignancy (CRC), 4 non-small cell lung malignancy (NSCLC), 5 endometrial malignancy, 6 and squamous-cell carcinoma of the top and throat (SCCHN). (bio-biz-navi.com)
  • 7 Another setting of EGFR activation in malignancy is usually activating somatic mutations that bring about constitutive kinase activity, and they are especially common in NSCLC (examined in Morgensztern examined the effectiveness of merging gefitinib with docetaxel in metastatic BC in comparison with docetaxel only. (bio-biz-navi.com)
  • Subsequently, lapatinib, an orally bioavailable small molecule dual HER2- and EGFR/HER1-specific tyrosine kinase inhibitor, received Food and Drug Administration (FDA) approval in combination with capecitabine for patients with advanced HER2+ breast cancer. (carcinogenesis.com)
  • EGFR protein expression and EGFR gene copy number were analysed by means of immunohistochemistry and fluorescence in situ hybridisation. (biomedcentral.com)
  • EGFR mutations were absent from squamous cell carcinoma of the anus and tonsils, but EGFR protein expression was detected in the majority of the cases. (biomedcentral.com)
  • Epidermal growth factor receptor (EGFR) has been validated as a therapeutic target in several human tumours, including colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (HNSCC). (biomedcentral.com)
  • Monoclonal antibodies directed against the extracellular domain of EGFR and small molecule inhibitors of the tyrosine kinase domain of the receptor have been evaluated in the treatment of several solid tumours including CRC, NSCLC and HNSCC [ 3 ]. (biomedcentral.com)
  • In NSCLC, approximately 85% of patients who responded favourably to gefitinib or erlotinib, two FDA-approved small-molecule EGFR-tyrosine-kinase inhibitors, were shown to have somatic mutations in the EGFR gene. (biomedcentral.com)
  • Several members of the Epidermal Growth Factor Receptor (EGFR) family, have been identified in the nucleus and nucleolus of many cancer cells, but their function in these compartments remains unexplored. (biomedcentral.com)
  • We focused our research on the nucleolar function that a specific member of EGFR family, the ErbB3 receptor, plays in glioblastoma, a tumor without effective therapies. (biomedcentral.com)
  • Since the EGFR signalling promotes proliferation in tumor the EGFR receptors often represent a marker of resistance with poor prognosis. (biomedcentral.com)
  • Receptor tyrosine-protein kinase erbB-2, also known as HER2/Neu (human epidermal growth factor receptor 2), is a member of the human epidermal growth factor receptor family. (meridianbioscience.com)
  • Overexpression of HER2/Neu plays an essential role in the development and progression of specific subtypes of breast cancer. (meridianbioscience.com)
  • ERBB2 is a protein that is also known as HER2 (human epidermal growth factor receptor 2). (antibodyguide.com)
  • The human protein is also frequently referred to as HER2 (human epidermal growth factor receptor 2) or CD340 (cluster of differentiation 340). (wikipedia.org)
  • But contrary to other members of the ERBB family, HER2 does not directly bind ligand. (wikipedia.org)
  • HER2 activation results from heterodimerization with another ERBB member or by homodimerization when HER2 concentration are high, for instance in cancer. (wikipedia.org)
  • HER2 is so named because it has a similar structure to human epidermal growth factor receptor, or HER1. (wikipedia.org)
  • Molecular cloning of the gene showed that HER2, Neu, and ErbB-2 are all encoded by the same orthologs. (wikipedia.org)
  • HER2 can heterodimerise with any of the other three receptors and is considered to be the preferred dimerisation partner of the other ErbB receptors. (wikipedia.org)
  • Signaling pathways activated by HER2 include: mitogen-activated protein kinase (MAPK) phosphoinositide 3-kinase (PI3K/Akt) phospholipase C γ protein kinase C (PKC) Signal transducer and activator of transcription (STAT) In summary, signaling through the ErbB family of receptors promotes cell proliferation and opposes apoptosis, and therefore must be tightly regulated to prevent uncontrolled cell growth from occurring. (wikipedia.org)
  • HER2 proteins have been shown to form clusters in cell membranes that may play a role in tumorigenesis. (wikipedia.org)
  • Receptor tyrosine-protein kinase ERBB-2 (HER2 - human epidermal growth factor receptor 2) is considered as a marker of aggressiveness in the case of breast cancer in primary tumours as well as in corresponding metastases. (biomedres.us)
  • In TGF-beta-treated MCF10A mammary epithelial cells overexpressing HER2 and by chromatin immunoprecipitation, we identified novel Smad targets including protein tyrosine phosphatase receptor type kappa (PTPRK). (nih.gov)
  • HER2 overexpression down-regulated its expression. (nih.gov)
  • Endogenous RPTPkappa associated with EGF receptor and HER2, resulting in suppression of basal and ErbB ligand-induced proliferation and receptor phosphorylation. (nih.gov)
  • Amplification of the human epidermal growth factor receptor 2 ( HER2 ) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. (wjgnet.com)
  • The degree of HER2 overexpression and amplification varies with the location of the carcinoma, with higher expression in the gastroesophageal and proximal parts compared to the distal parts of the stomach. (wjgnet.com)
  • Further, HER2 overexpression and amplification also seems to be related to the Lauren histological classification, with higher levels found in the intestinal phenotype compared to the diffuse and mixed types. (wjgnet.com)
  • The prognostic properties of HER2 overexpression and amplification are still under debate, but a large number of studies seem to indicate that HER2 is a negative prognostic factor. (wjgnet.com)
  • Patients with a strong overexpression of the HER2 protein (IHC3+) specifically benefited from the treatment, with a median overall survival of 17.9 mo. (wjgnet.com)
  • HER2 positive breast cancer is identified by the overexpression of human epidermal growth factor receptor-2 (HER2) protein in tumor tissue and results in an increased rate of cell proliferation. (her2support.org)
  • This membrane deformation will not need receptor signalling actions, but outcomes from the high degrees of HER2 in the cell surface area. (president2010.info)
  • HER2 is certainly a CAY10471 Racemate known person in the ErbB/HER receptor tyrosine kinase family members1,2,3. (president2010.info)
  • HER2 BC cells using a 3+ immunohistochemistry (IHC) rating display high basal degrees of receptor kinase activity and phosphorylation, and these induce CAY10471 Racemate constitutive activation from the mitogen-activated proteins phosphatidylinositol and kinase 3-kinase/Akt pathways8. (president2010.info)
  • These features of HER2 overexpression had been acquired from several ensemble experiments, where receptor actions are averaged more than an extremely large numbers of cells typically. (president2010.info)
  • These observations claim that a non-canonical aftereffect of HER2 overexpression is available that plays a part in the disruption of epithelial features exhibited in HER2 3+ BC cells14, Mouse monoclonal to EphA5 which is certainly implicated in early-stage cancers development15,16. (president2010.info)
  • A lot of area points of specific HER2s had been obtained by monitoring one receptors (for 100?s in a 10.72?Hz acquisition price) labelled with anti-HER2 Fab:QD (H2Fab:QD) conjugates using total inner reflection fluorescence microscopy (TIRFM)13. (president2010.info)
  • We initial likened the receptor distribution patterns inside the same cell type where HER2 appearance levels had been artificially changed. (president2010.info)
  • The HER2 receptor does not bind to any known ligands, however, its dimerization arm is innately positioned in an open conformation. (plos.org)
  • Omdat bij 70% van de alvleesklierkankerpatiënten de HER2-Neu expressie oververtegenwoordigd is en juist Herceptin bij borstkankerpatiënten met deze receptor uitstekende resultaten laat zien zijn deze trials opgezet. (kanker-actueel.nl)
  • HER2 gene encodes a cell-surface glycoprotein tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor. (biovisi.com)
  • HER2 is an oncogene and overexpression of unaltered HER2 coding sequences in NIH 3T3 cells results in cellular transformation and tumorigenesis. (biovisi.com)
  • HER2 is amplified in about 30% of primary human breast malignancies and overexpression of HER2 is associated with the most aggressive tumors that show uncontrolled proliferation, resistance to apoptosis and increased motility. (biovisi.com)
  • Tumor Her2/ neu is generally assessed as protein overexpression by using immunohistochemistry (IHC), and patients with tumors that either have 2+ or 3+ results with this method become good candidates for treatment with trastuzumab. (biomedcentral.com)
  • It is also frequently called HER2 (from human epidermal growth factor receptor 2 ) or HER2/neu . (iiab.me)
  • HER2 does not have any identified ligand an undeniable fact explained from the structure from the extracellular area from the receptor which is already in an activated conformation and does not allow ligand docking. (ecolowood.com)
  • With the addition of trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), improvements in overall survival have been observed among patients with advanced HER2-positive disease. (carcinogenesis.com)
  • One type of breast cancer is identified by the human epidermal growth factor receptor 2 (HER2) gene amplification. (carcinogenesis.com)
  • HER2 is a member of the cErbB family of receptor tyrosine kinases, and is responsible for HER2-mediated signal transduction in the cytoplasm. (carcinogenesis.com)
  • The human epidermal growth factor receptor 2 (HER2) status is important in the medical management of patients with various human cancers. (ijmpo.org)
  • The proto-oncogene designated erbB2 or HER2 encodes a 185-kilodalton transmembrane tyrosine kinase (p185erbB2), whose overexpression has been correlated with a poor prognosis in several human malignancies. (embl.de)
  • Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ERBB2 gene. (wikipedia.org)
  • In particular, the overexpression of ERBB2 enhances the properties of tumour cells associated with increased cancer metastasis (invasiveness, angiogenicity, enhanced survival). (biomedres.us)
  • The enhancement in metastatic properties was also found to occur via activation of ERBB2 receptor signaling pathways [2]. (biomedres.us)
  • In addition, it has also been shown that the level of fibronectin, a blood clotting associated protein is significantly increased in ERBB2-overexpressing MDA-MB231 cells [7]. (biomedres.us)
  • These reports led us to consider as a working hypothesis whether the overexpression of ERBB2 is able to establish a procoagulant disorder in cancer. (biomedres.us)
  • It was observed that overexpression of ERBB2 was able to modulate the level of several coagulation proteins, including protein C, Factor-X and TF, and the activities of TF and thrombomodulin, as well as the rate of clotting and thrombin activity. (biomedres.us)
  • Such effects were found to be mediated by PI3k/ Akt signaling pathways since the increased these ERBB2 sensitive coagulation proteins in a way that was commensurate with the activity of p-ERK and p-Akt. (biomedres.us)
  • In line with this conclusion it was also observed that the expression of coagulation proteins corresponded with the level of expression of ERBB2 in three 'native' breast cancer cell lines (human enriched breast cancer stem cell (CSC), MDA-MB231 and MCF-7). (biomedres.us)
  • The finding is the first time shown pro-tumour gene ERBB2 enable to modulate coagulation protein expression and clotting kinetics in breast cancer cells, it is via the PI3k/Akt pathways, which further supports the proposal that the state of the coagulation system in cancer is directly influenced by oncogenic transformation. (biomedres.us)
  • ErbB2 belongs to the ErbB family of receptor tyrosine kinases, which has been implicated in a variety of human cancers , including cancers of the breast. (her2support.org)
  • Receptor tyrosine-protein kinase erbB-2 , also known as CD340 (cluster of differentiation 340), proto-oncogene Neu , Erbb2 (rodent), or ERBB2 (human), is a protein that in humans is encoded by the ERBB2 gene. (iiab.me)
  • Activation of Src by protein tyrosine phosphatase 1B Is required for ErbB2 transformation of human breast epithelial cells. (musc.edu)
  • This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. (creativebiolabs.net)
  • The overexpression of the erbB-2 proto-oncogene is associated with an aggressive human adenocarcinomas, mainly breast and ovarian tumours. (australbiologicals.com)
  • The Her-2/ neu proto-oncogene, also known as c-erbB-2, is a member of the type I growth factor receptor gene family and is located in the long arm of chromosome 17 (17q12-21.32) [ 1 ]. (biomedcentral.com)
  • A basic helix-loop-helix leucine zipper (bHLHZ) transcription factor and proto-oncogene protein that functions in cell growth and proliferation. (bvsalud.org)
  • Phosphorylated tyrosine residues recruit various intracellular adaptor and effector molecules that result in the propagation of growth promoting signal transduction cascades [1] , [2] . (plos.org)
  • Some of the new approaches depend on tumor biology and aim specifically to inhibit tumor growth and metastasis by targeting the tumor microenvironment or vasculature (leaving normal cells unaffected) or focusing on specific protein or signal transduction pathways. (medscape.com)
  • Recently, several novel agents targeting growth factor receptors, angiogenic pathways, adhesion molecules and mediators of intracellular signal transduction have been clinically explored. (docksci.com)
  • Following dimerization there is increased intracellular kinase activity of the receptor through a proximity effect resulting in phosphorylation of critical tyrosine residues on the cytoplasmic domain which then triggers the signal transduction cascade. (ecolowood.com)
  • It first binds with high affinity to specific cell-surface receptors and then induces their dimerization, which is essential for activating the tyrosine kinase in the receptor cytoplasmic domain, initiating a signal transduction that results in DNA synthesis and cell proliferation. (embl.de)
  • Novel therapeutic agents, in particular those that specifically target members of the human epidermal growth factor receptor (HER (ErbB1)) pathway, have shown encouraging therapeutic efficacy. (bmj.com)
  • Amplification and overexpression of this gene are also associated with multiple human cancers. (creativebiolabs.net)
  • Gene amplification and overexpression of the proteins in breast malignancies (BCs) anticipate poor disease final result due to raised metastatic potentials4,5,6,7. (president2010.info)
  • Amplification of the ErbB-2 gene and overexpression of its product has been detected in almost 40% of primary human breast tumors, which correlates with poor prognosis in node positive breast cancer. (activemotif.com)
  • Amplification of the HER-2 gene with overexpression of the protein occurs in 20-30% of breast cancers, and tumor progression in mammary cancer is associated with elevated levels of tyrosine-phosphorylated neu and erbB-3. (ihcworld.com)
  • Amplification and overexpression of the neu gene have been found in several human adenocarcinomas. (prinsesmaximacentrum.nl)
  • In 20-30% of breast carcinomas, Her-2/ neu status is altered, and this is manifested either as amplification of the gene or overexpression of the protein product [ 3 ]. (biomedcentral.com)
  • Nevertheless, a negative (0 or 1+) or a 3+ Her-2/ neu IHC correlates well with a negative or positive Her-2/ neu gene amplification, respectively. (biomedcentral.com)
  • Her-2/ neu gene amplification is primarily detected by in situ hybridization and uses fluorescence (FISH) to detect the signals. (biomedcentral.com)
  • CISH is potentially able to detect Her-2/ neu gene amplification and to minimize, if not eliminate, the false positive fraction with the IHC procedure. (biomedcentral.com)
  • Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. (arigobio.com)
  • Phosphatidylinositol 3-kinase recruitment by p185erbB-2 and erbB-3 is potently induced by neu differentiation factor/heregulin during mitogenesis and is constitutively elevated in growth factor-independent breast carcinoma cells with c-erbB-2 gene amplification. (musc.edu)
  • The HER (erbB) family of transmembrane receptor tyrosine kinases is one of the cytostatic targets in tumor cell growth and survival. (medscape.com)
  • This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. (arigobio.com)
  • MEN1 maps on chromosome 11 and encodes for menina, a nuclear protein involved in cell replication, DNA repair and transcription process. (springeropen.com)
  • It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. (cancerindex.org)
  • The prostaglandin-endoperoxide synthase 2 gene (PTGS2), which encodes cyclooxygenase-2, was found to upregulate the expression of TGF-β2 ( 14 ). (spandidos-publications.com)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • This locus, however, also encodes a protein from an alternative reading frame, designated p19ARF. (medscape.com)
  • 25 Furthermore to kinase inhibitors, medical tests have also examined the addition of the ligand obstructing monoclonal antibody cetuximab towards the DNA-alkylating agent carboplatin. (bio-biz-navi.com)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • Dimerisation results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways. (wikipedia.org)
  • Its structure consists of an extracellular ligand-binding website a Alosetron single transmembrane hydrophobic helix and a cytoplasmic carboxy-terminal website to which tyrosine kinase activity is definitely limited.1 HER receptors are usually located in the basolateral membrane of the epithelial cells where they can interact with their ligands present in the stroma thus mediating signaling between the epithelium and the extra-cellular matrix. (ecolowood.com)
  • Generally, these receptors explain their function on the cell membrane where, after the binding with growth factors or neuregulin undergo to homo or hetero oligomerization with the activation of the intrinsic tyrosine kinase activity and the subsequent recruitment of proteins involved in the cytoplasmic signalling pathways. (biomedcentral.com)
  • Combining these new datasets with existing published gene expression and protein expression data have identified selected panels of novel biomarkers which have been evaluated on over 100 cervical cancer and pre-cancer cases using standard immunohistochemistry approaches. (europa.eu)
  • Once the ligand binds to the extracellular domain the receptor undergoes a conformational change of this region which allows homodimerization or heterodimerization with another activated receptor of the HER family. (ecolowood.com)
  • A common feature of all EGF-like domains is that they are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase). (embl.de)
  • The encoded protein possesses an extracellular domain which is composed of two immunoglobulin-like motifs at the N-terminal, followed by two fibronectin type-III motifs. (cancerindex.org)
  • Each FACE ErbB-2 Kit provides 96 rxns each of 2 antibodies that enable you to monitor and compare the levels of both phosphorylated and total ErbB-2. (activemotif.com)
  • We have obtained monoclonal antibodies to the human neu protein by immunizing a Balb/c mouse with a Balb/c cell line expressing the human neu gene by transfection. (prinsesmaximacentrum.nl)
  • The monoclonal antibodies reacted with neu protein on intact cells by immunofluorescence and immunoprecipitated neu in metabolically labeled cells, also in the presence of tunicamycin. (prinsesmaximacentrum.nl)
  • We tested possible down-modulating effects of these monoclonal antibodies on SKBR-3 mammary tumor cells, which express high levels of wild-type human neu protein. (prinsesmaximacentrum.nl)
  • In contrast, the antibodies induced 50-65% down-modulation in NIH3T3 cells expressing the mutated human neu protein and could inhibit these cells to form colonies in soft agar. (prinsesmaximacentrum.nl)
  • Mouse monoclonal antibodies are purified protein A or G and can be conjugated to FITC for flow cytometry or FACS and can be of different isotypes.Rabbits are used for polyclonal antibody production by Biovision. (biovisi.com)
  • Familial AD (FAD) cases are caused by autosomal dominant mutations in the genes for amyloid precursor protein (APP) and the presenilins (PS1 and PS2) ( Sisodia and St George-Hyslop, 2002 ). (jneurosci.org)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • published on the web 30 OctoberINTRODUCTION The important mechanisms that cause a constitutive activation of the PI3KAkt pathway are mutations and overexpression of upstream receptor tyrosine kinases which include erbB family members members, activating mutations of PIK3CA or RAS along with the loss of tumor suppressor protein phosphatase and tensin homolog (PTEN).1 Akt, also referred to as protein kinase B (PKB), consists of three isoforms: PKBAkt1, PKBAkt2 and PKBAkt3. (bet-bromodomain.com)
  • The FACE ErbB-2 (Y877) Kit contains a phospho-ErbB-2 antibody that was raised in rabbit against a synthetic phospho-peptide corresponding to residues surrounding phosphorylated Tyr877 of human ErbB-2 and recognizes ErbB-2 only when phosphorylated at Tyr877. (activemotif.com)
  • This process leads to the activation of each receptors' tyrosine kinase and the subsequent phosphorylation of tyrosine residues located on their C-terminal tails. (plos.org)
  • Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit (Probable). (arigobio.com)
  • Ligand-binding increases phosphorylation on tyrosine residues (PubMed:27134172). (arigobio.com)
  • A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermal growth factor (EGF) has been shown [ ( PUBMED:2288911 ) ( PUBMED:6334307 ) ( PUBMED:6607417 ) ( PUBMED:3282918 ) ] to be present, in a more or less conserved form, in a large number of other, mostly animal proteins. (embl.de)
  • This family of RTKs has been highly implicated in the formation and progression of various cancers via aberrant overexpression, kinase activation, and mutation [1] , [2] . (plos.org)
  • Thirty samples were sequenced for K-RAS exon 2 and no mutation was identified. (biomedcentral.com)
  • Genetic mutation promotes biological evolution and results in biodiversity ( 2 , 3 ). (spandidos-publications.com)
  • In summary, signaling through the ErbB family of receptors promotes cell proliferation and opposes apoptosis, and therefore must be tightly regulated to prevent uncontrolled cell growth from occurring. (iiab.me)
  • Our previous study has shown that CCAAT-enhancer binding protein β (C/EBPβ) is an important regulator in METH-induced neuronal autophagy and apoptosis. (cancerindex.org)
  • PTEN/MMAC1 overexpression decreases insulin-like growth factor-I-mediated protection from apoptosis in neuroblastoma cells. (musc.edu)
  • However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. (arigobio.com)
  • The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. (cancerindex.org)
  • Over-expression of the c-erbB-2 oncogene occurs in a proportion of human adenocarcinomas and in breast carcinoma is associated with poorer prognosis. (nih.gov)
  • Sections of formalin-fixed, paraffin-embedded tumour tissue from 22 patients with mammary and extramammary Paget's disease have been stained immunohistochemically using a monoclonal antibody (NCL-CB11) raised against a synthetic peptide from the C-terminal end of the predicted sequence of the c-erbB-2 protein product. (nih.gov)
  • EphB4 is a membrane-bound receptor tyrosine kinase (RTK) commonly over-produced by many epithelial cancers but with low to no expression in most normal adult tissues. (oncotarget.com)
  • 60 identical and the kinase domains are a lot more than 85 identical.three Catalytically active Akt regulates the function of numerous substrates involved in cell survival, development, proliferation, metabolism and protein synthesis (reviewed in Manning, Cantley4). (bet-bromodomain.com)
  • These results highlight the potential role for the nucleolar ErbB3 receptor, as a new target in glioblastoma. (biomedcentral.com)
  • Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. (creativebiolabs.net)
  • Classically, HER family members function from the cell surface, where binding to cognate ligands can induce receptor homo- or hetero-dimerization with other HER family receptors [3] . (plos.org)
  • Tyr is the phosphorylation site that is most tightly linked to oncogenic transformation and coupling to the ras/MAP kinase signaling pathway. (ihcworld.com)
  • The exact biological mechanism(s) by which the BBB limits drug exposure is not clear, but in addition to epithelial tight junctions, enhanced efflux of chemotherapeutic agents out of the CNS space by endothelial cell membrane transporters in brain blood vessels plays a primary role ( 2 ). (jcancer.org)
  • erbB-2 overexpression in human mammary epithelial cells confers growth factor independence. (musc.edu)
  • Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells. (musc.edu)
  • Cooperative interactions of HER-2 and HPV-16 oncoproteins in the malignant transformation of human mammary epithelial cells. (musc.edu)
  • By contrast, the 10 downregulated genes were primarily associated with epithelial membrane proteins ( 11 ). (spandidos-publications.com)
  • Breast cancer is one of the most common primary tumors to develop associated brain metastases ( 1 , 2 ), and while recent progress in cancer therapy has improved control of primary breast tumors, methods to effectively treat brain metastases from breast cancer remain inadequate. (jcancer.org)
  • We assessed Her-2/ neu alteration using CISH on formalin-fixed paraffin-embedded primary invasive ductal carcinoma tumors in which IHC (CB11 antibody) had previously been performed, and we compared the results with IHC. (biomedcentral.com)
  • Similarly, although the small group of well-differentiated tumors was apparently Her-2/ neu negative in both tests, no significant association was noted between any tumor histologic grade and either IHC or CISH results. (biomedcentral.com)
  • 1 ] [ 2 ] These tumors develop more in middle and late adulthood. (ijmpo.org)
  • 3 ] Most meningiomas are benign tumors, but up to 15% are atypical, and 2% malignant according to the World Health Organization histological criteria reported in 2016. (ijmpo.org)
  • Rapid growth and division of cells in tumors are correlated with intensive nucleolar metabolism as a response to oncogenic factors overexpression. (biomedcentral.com)
  • An important development in cancer research over the past 2 decades has been the recognition that genetic changes drive the pathogenesis of tumors of both adulthood and childhood. (medscape.com)
  • [ 2 ] Targeted disruption of TP53 in the mouse leads to the development of various tumors (see image below). (medscape.com)
  • IgG fraction from rabbit polyclonal antibody obtained by immunizing rabbits with a synthetic peptide (AENPEYLGLDVPV) corresponding to amino acids 1243-1255 of human c-erbB-2/HER-2/neu oncoprotein. (australbiologicals.com)
  • C-erbB-2 oncoprotein is a 185 kDa type I membrane tyrosine kinase receptor and belongs to the EGF receptor family. (australbiologicals.com)
  • About 5% of breast carcinomas are positive for phospho-c- erb B-2/HER-2/ neu oncoprotein. (ihcworld.com)
  • The primary antihuman antibody against c-erbB-2 oncoprotein (DAKO Diagnostics) was used for IHC. (ijmpo.org)
  • Therefore, we utilized quantum dot (QD)-structured single-receptor monitoring and analysis strategies in live cells to research whether a spatial control exists that may impact the activation of overexpressed HER2s in BC cells. (president2010.info)
  • Following stimulation, the cells are fixed rapidly, which preserves activation-specific protein modifications. (activemotif.com)
  • Activation of HER-2 is frequent in ductal carcinoma in situ suggesting that HER-2 signaling plays a critical role in the early stages of breast tumorigenesis. (ihcworld.com)
  • The effect of over expression on the synthesis and activities of selected blood coagulation proteins was determined as well as relevant signaling pathways. (biomedres.us)
  • Membrane-bound HER receptors activate numerous tumor promoting signaling cascades via this mechanism, including the PI3K/AKT, Ras/Raf/Mek/Erk, PLCγ/PKC, and signal transducer and activator of transcription (STAT) pathways [1] , [2] . (plos.org)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. (cancerindex.org)
  • Nuclear localized HER family receptor tyrosine kinases (RTKs) have been observed in primary tumor specimens and cancer cell lines for nearly two decades. (plos.org)
  • Brand TM, Iida M, Luthar N, Wleklinski MJ, Starr MM, Wheeler DL (2013) Mapping C-Terminal Transactivation Domains of the Nuclear HER Family Receptor Tyrosine Kinase HER3. (plos.org)
  • erbB family receptor expression and growth regulation in a newly isolated human breast cancer cell line. (musc.edu)
  • The ErbB family consists of four individual plasma membrane-bound receptor tyrosine kinases. (wikipedia.org)
  • All 12 cases of mammary Paget's disease showed membrane staining of intra-epidermal cells, indicating c-erbB-2 over-expression. (nih.gov)
  • Both the receptor and the ligand are membrane-bound but usually expressed on neighbouring cells. (oncotarget.com)
  • Fast Activated Cell-based ELISA (FACE™) Kits provide a simple, sensitive method for detecting protein phosphorylation directly in the cell, without making extracts or performing electrophoresis and membrane blotting. (activemotif.com)
  • While the classical membrane-bound functions of HER family RTKs have been extensively studied, accumulating data suggest that these receptors can be found in the cell's nucleus where they can function as co-transcriptional activators [4] , [5] . (plos.org)
  • Key drug efflux transporters operational in preserving the BBB are the P-glycoprotein (Pgp) transporter, which belongs to the ATP-binding cassette (ABC) transporter family, and the breast cancer resistance protein (BCRP) ABCG2 ( 4 , 5 ). (jcancer.org)
  • Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. (arigobio.com)
  • Of the 31 genes, the 21 upregulated genes were primarily associated with cell paracrine and intracellular signaling, transcription regulation and cell adhesion and migration, and their transcriptional products included transforming growth factor-β2 (TGF-β2), insulin-like growth factor-binding protein 2 and transcriptional factor AP-2α/γ ( 11 ). (spandidos-publications.com)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • This protein has no ligand binding domain of its own and therefore cannot bind growth factors. (arigobio.com)
  • 1 ErbB users type homo- and heterodimeric cell-surface receptors with original extracellular domains yielding ligand-binding specificity. (bio-biz-navi.com)
  • Substitution of a valine for a glutamic acid or a glutamine in the transmembrane domain can result in the constitutive dimerisation of this protein in the absence of a ligand. (wikipedia.org)
  • Anti-rabbit IgG (H+L), F(ab')2 Fragment (Alexa Fluor ® 488 Conjugate) #4412 was used as a secondary antibody. (cellsignal.com)
  • Peptide exclusion was used to identify the epitope targeted by this antibody within the cysteine-rich region of the EphB4 protein, a sequence defined as a potential ligand interacting interface. (oncotarget.com)
  • Addition of antibody to cancer cells resulted in phosphorylation and subsequent degradation of the EphB4 protein, suggesting a mechanism that is ligand mimetic and tumour suppressive. (oncotarget.com)
  • The Y877 kit contains phospho-ErbB-2 antibody that recognizes ErbB-2 only when phosphorylated at Tyr877, while the Y1248 kit provides a phospho-antibody that recognizes ErbB-2 only when phosphorylated at Tyr1248. (activemotif.com)
  • Each kit contains a total-ErbB-2 antibody that recognizes ErbB-2 regardless of its phosphorylation state. (activemotif.com)
  • Each well is then incubated with a primary antibody specific for the activated protein of interest. (activemotif.com)
  • FACE Kits also contain primary antibody specific for the native inactive protein, so you can monitor both native and activated protein levels in the same experiment. (activemotif.com)
  • This polyclonal antibody can be used in ELISA (1: 100 dilution), immunocytochemistry (1: 100 dilution) and it recognizes c-erbB-2 protein (185 kDa) in Western Blot of HeLa cell lysate (1: 500 dilution). (australbiologicals.com)
  • This cell surface receptor can be targeted specifically by the neutralizing antibody Herceptintrade mark. (kanker-actueel.nl)
  • For continuous use, store undiluted antibody at 2-8°C for up to a week. (arigobio.com)
  • Cases of invasive breast carcinoma with the phosphorylated receptor have displayed aggressive clinicopathological features and adverse prognoses. (ihcworld.com)
  • all nine tumours were c-erbB-2 positive and in eight the in situ component was of comedo or solid type. (nih.gov)
  • AXL, a tyrosine kinase receptor, is commonly overexpressed in several solid tumours and numerous hematopoietic malignancies including acute myeloid leukaemia, acute lymphocytic leukaemia, chronic myeloid leukaemia, chronic lymphocytic leukaemia and multiple myeloma. (cancerindex.org)