• Recently, we isolated a novel negative regulator of epidermal growth factor receptor (EGFR), termed EGFR-related protein (ERRP), whose expression attenuates EGFR activation. (aacrjournals.org)
  • The transcription factor FOSL1 (also known as Fra-1), which is found in basal-like breast cancers but not in the luminal subtype, stimulated the transcription of miR-221/222, and the abundance of these miRNAs decreased with inhibition of the epidermal growth factor receptor (EGFR) or MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase), placing miR-221/222 downstream of the RAS pathway. (nih.gov)
  • The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. (wikipedia.org)
  • The ErbB protein family consists of 4 members ErbB-1, also named epidermal growth factor receptor (EGFR) ErbB-2, also named HER2 in humans and neu in rodents ErbB-3, also named HER3 ErbB-4, also named HER4 v-ErbBs are homologous to EGFR, but lack sequences within the ligand binding ectodomain. (wikipedia.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)
  • Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis. (nature.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)
  • 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 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)
  • The objective of this study was to determine the conversion rate of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) between primary tumors and metastatic lesions in advanced breast cancer. (springer.com)
  • The status of human epidermal growth factor receptor 2 (HER2) and the hormone receptors (HR), including estrogen receptor (ER) and progesterone receptor (PR), are the most relevant biomarkers for clinical practice, predicting response to anti-HER2 and endocrine therapies, respectively. (springer.com)
  • It selectively inhibits erbB1 (epidermal growth factor receptor), erbB2, erbB3, and erbB4 without blocking tyrosine kinase activity of many other receptors such as platelet-derived growth factor receptor, fibroblast growth factor receptor, and insulin receptor. (lclabs.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 HER2 receptor does not bind to any known ligands, however, its dimerization arm is innately positioned in an open conformation. (plos.org)
  • Being aware of the benefits that the correct systemic therapy provides to patients with advanced breast cancer, the Spanish Breast Cancer Research Group (GEICAM) performed a prospective, observational study to determine the conversion rate of receptor status (ER, PR and HER2) between the primary tumor and the recurrent lesion. (springer.com)
  • Analizar las diferencias en la presentación de variables clínico-patológicas, de acuerdo con la expresión proteica de GRB7, en tumores HER2 positivos en mujeres colombianas con cáncer de mama invasivo, diagnosticado entre los años 2013 y 2015 en el Instituto Nacional de Cancerología E.S.E (INC). Métodos. (bvsalud.org)
  • Se evaluó la expresión de los receptores hormonales (receptor de estrógeno (RE) y de progesterona (RP)), HER2, Ki67 y GRB7, mediante inmunohistoquímica (IHQ), y a partir de estos, se clasificaron los tumores en subtipos intrínsecos. (bvsalud.org)
  • A single pathologist evaluated the protein expression of hormone receptors (estrogen (ER) and progesterone receptor (PR)), HER2, Ki67, and GRB7 by immunohistochemistry (IHC). (bvsalud.org)
  • In the current study, we examined the effects of recombinant ERRP on the growth and ligand-induced activation of multiple members of erbB family in three pancreatic cancer cell lines that express varying levels of EGFR and other member(s) of its family, specifically HER-2. (aacrjournals.org)
  • ERRP also inhibited ligand-induced activation of EGFR, HER-2, and HER-3 (ErbB3). (aacrjournals.org)
  • In contrast, Erbitux and Herceptin only partially or modestly inhibited activation of EGFR, HER-2, and HER-3. (aacrjournals.org)
  • Nodal positivity correlated with histological grade and tumour size, but not with estrogen receptor or c-erbB-2 status. (ispub.com)
  • Results of estrogen receptor and c-erbB-2 status using immunohistochemistry were documented. (ispub.com)
  • Chi square was used to test the association between ethnic group, tumour size (categorized as ≤2 cm, >2 cm and ≤5 cm, and >5 cm), histological grade, estrogen receptor (ER) status, c-erbB-2 status and lymph node metastases. (ispub.com)
  • Cancer cells that have estrogen receptors are referred to as estrogen receptor-positive (ER-positive) cancers. (texasoncology.com)
  • Furthermore, a new of drugs called estrogen-receptor antagonists work in a similar way as tamoxifen and have been shown to benefit some patients with breast cancer. (texasoncology.com)
  • Like SERMs, estrogen receptor antagonists work by preventing estrogen from stimulating the growth of estrogen receptor-positive cells. (texasoncology.com)
  • Binding of Sema4D to plexin-B1 stimulates the intrinsic tyrosine kinase activity of ErbB-2, resulting in the phosphorylation of both plexin-B1 and ErbB-2. (rupress.org)
  • Our data indicate that ErbB-2 is an important component of the plexin-B receptor system and that ErbB-2-mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation, which underlies cellular phenomena downstream of plexin-B1, including axonal growth cone collapse. (rupress.org)
  • The intracellular/cytoplasmic region of the ErbB receptor consists mainly of three subdomains: A juxtamembrane with approximately 40 residues, a kinase domain containing approximately 260 residues and a C-terminal domain of 220-350 amino acid residues that become activated via phosphorylation of its tyrosine residues that mediates interactions of other ErbB proteins and downstream signaling molecules. (wikipedia.org)
  • Lapatinib inhibited phosphorylation of ErbB receptors and also reduced the level of phosphorylated AKT. (edu.kz)
  • In RT112 cells, which express high levels of ErbB receptors and harbour wild-type p53, combined GTC/lapatinib treatment resulted in the phosphorylation of p53 at Ser46 and accumulation of sub-G 1 cell populations. (edu.kz)
  • 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)
  • It not only inhibits tyrosine phosphorylation but also enhances ubiquitinylation and accelerates endocytosis and subsequent intracellular destruction of ErbB-2 molecules. (lclabs.com)
  • Canertinib inhibited erbB receptor phosphorylation and induced growth inhibition and apoptosis at concentrations of 1 µM or more. (lclabs.com)
  • Essential erbB family phosphorylation in osteosarcoma as a target for CI-1033 inhibition. (lclabs.com)
  • LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation. (nature.com)
  • Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy. (lclabs.com)
  • The gene symbol, ErbB, is derived from the name of a viral oncogene to which these receptors are homologous: erythroblastic leukemia viral oncogene. (wikipedia.org)
  • Here, we show that the dual inhibitor of ErbB receptors, lapatinib, enhances cytostatic and induces cytotoxic effects of GTC in two bladder cancer cell lines which differ with regard to expression levels of proteins taking part in the ErbB pathway. (edu.kz)
  • As ErbB-family ligands and receptors are highly expressed within the stem-cell niche 7 , we hypothesize that strong endogenous regulators must control the pathway in the stem-cell compartment. (nature.com)
  • Figure 4: Lrig1 controls endogenous signalling through the ErbB pathway. (nature.com)
  • The degradative pathway of ErbB receptor tyrosine kinases stimulated by tyrosine kinase inhibitors appears to be chaperone mediated, and thus is similar to the pathways activated by the heat shock protein 90 (Hsp90) antagonist geldanamycin and by stress-induced mechanisms. (lclabs.com)
  • The figure below shows the tridimensional structure of the ErbB family proteins, using the pdb files 1NQL (ErbB-1), 1S78 (ErbB-2), 1M6B (ErbB-3) and 2AHX (ErbB-4): The four members of the ErbB protein family are capable of forming homodimers, heterodimers, and possibly higher-order oligomers upon activation by a subset of potential growth factor ligands. (wikipedia.org)
  • 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)
  • Notably, the ErbB1 and ErbB4 are the two most studied and intact among the family of ErbB proteins, Which forms functional intracellular tyrosine kinases. (wikipedia.org)
  • The ability ('+') or inability ('-') of each growth factor to activate each of the ErbB receptors is shown in the table below: The dimerization occurs after ligand bind to the extracellular domain of the ErbB monomers and monomer-monomer interaction establishes activating the activation loop in a kinase domain, that activates the further process of transphosphorylation of the specific tyrosine kinases in the kinase domain of ErbB's intracellular part. (wikipedia.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)
  • In addition to plexins, various other proteins have been implicated either as receptors for semaphorins or as components of the semaphorin receptor complex ( Pasterkamp and Kolodkin, 2003 ). (rupress.org)
  • Blinded determinations of receptor status on paired samples were performed by immunohistochemistry and fluorescence in situ hybridization at a central laboratory and compared with those performed locally. (springer.com)
  • ErbB-1 and ErbB-2 are found in many human cancers, and their excessive signaling may be critical factors in the development and malignancy of these tumors. (wikipedia.org)
  • Canertinib (CI-1033, PD 183805) is a pan-erbB tyrosine kinase inhibitor. (lclabs.com)
  • Radiosensitization by pan ErbB inhibitor CI-1033 in vitro and in vivo. (lclabs.com)
  • The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases. (nature.com)
  • A dominant-negative form of ErbB-2 blocks Sema4D-induced RhoA activation as well as axonal growth cone collapse in primary hippocampal neurons. (rupress.org)
  • For the activation of kinase domain in the ErbB dimer, asymmetric kinase domain dimer of the two monomers is required with the intact asymmetric (N-C lobe) interface at the site of adjoining monomers. (wikipedia.org)
  • Activation of the tyrosine kinase domain leads to the activation of the whole range of downstream signaling pathways like PLCγ, ERK 1/2, p38 MAPK, PI3-K/Akt and more with the cell. (wikipedia.org)
  • Our findings reveal ErbB activation as a strong inductive signal for stem-cell proliferation. (nature.com)
  • Figure 5: Lrig1 controls ErbB activation in vivo . (nature.com)
  • 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)
  • Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member. (bvsalud.org)
  • Given that receptor tyrosine kinases of the ErbB family are overexpressed in a high proportion of metastatic bladder tumours, approaches involving small-molecule inhibitors of ErbB receptors in combination with conventional cytostatic drugs are of potential interest. (edu.kz)
  • The HER (erbB) family of transmembrane receptor tyrosine kinases is one of the cytostatic targets in tumor cell growth and survival. (medscape.com)
  • Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease, while excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. (wikipedia.org)
  • Excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. (wikipedia.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)
  • 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)
  • In spite of the relevance of receptor status, the choice of systemic treatment for advanced disease is more often based on the biological characteristics of the primary tumor at the time of initial diagnosis than of the recurrent lesion at the time of relapse. (springer.com)
  • The fetal lung 2: Pulmonary hypoplasia. (medscape.com)
  • The pressure in the fetal trachea is normally about 2 mm Hg higher than in the amniotic fluid, thus preventing outflow of fetal lung fluid. (medscape.com)
  • Therefore, the expression of a number of growth factors and their receptors, all of which affect fetal lung development, is temporally and spatially regulated. (medscape.com)
  • VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen. (medscape.com)
  • Kutasy B, Friemacher F, Duess JW, Puri P. Prenatal administration of retinoic acid increases the trophoblastic insulin-like-growth factor 2 protein expression in the nitrofen model of congenital diaphragmatic hernia. (medscape.com)
  • BT-474 cells, obtained expression of the receptor has important implications for their biology from American Type Culture Collection, were maintained in RPMI 1640 and therapy (1). (lu.se)
  • This has implications for our understanding of ErbB signalling in tissue development and maintenance and the progression of malignant disease. (nature.com)
  • The erbB family of receptor tyrosine kinases plays critical roles in human cancers, including pancreatic cancer. (aacrjournals.org)
  • by blocking the estrogen receptors so that estrogen cannot bind and stimulate growth-related activity in breast and other cells. (texasoncology.com)
  • 2 , 3 , 4 Femara and Arimidex are nonsteroidal aromatase inhibitors that bind reversibly to aromatase. (texasoncology.com)
  • There are 11 growth factors that activate ErbB receptors. (wikipedia.org)
  • Lastly, the impact of receptor discordance on the choice of subsequent systemic treatment was assessed. (springer.com)
  • With the technological advances, we are able to characterize molecular subtypes [2] , [3] of breast cancer which has facilitated the development of molecularly targeted therapeutics. (carcinogenesis.com)
  • The current study aimed to map the putative transactivation domains (TADs) of the HER3 receptor. (plos.org)
  • To understand how the B 1 and B 2 regions influenced the transcriptional functions of nuclear HER3, we performed cyclin D1 promoter-luciferase assays in which HER3 deleted of the B 1 and B 2 regions was severely hindered in regulating this promoter. (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)
  • Reasons for non-evaluability included the inability to perform biopsy ( n = 4) or biopsy results showing normal tissue ( n = 3), benign disease ( n = 3) or a second neoplasia ( n = 2). (springer.com)
  • In ErbB-3 receptor mutant mice, they have less severe defects in the heart and thus are able to survive longer throughout embryogenesis. (wikipedia.org)
  • Discovering a specific agent, which targets multiple members of the erbB family, would be important in pancreatic cancer therapy. (aacrjournals.org)
  • Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. (rupress.org)
  • All four ErbB receptor family members are nearly same in the structure having single-chain of modular glycoproteins. (wikipedia.org)
  • 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)
  • ErbB protein family signaling is important for development. (wikipedia.org)
  • It is a complex process due to the domain specificity and nature of the members of ErbB family. (wikipedia.org)
  • The disease is associated with high morbidity and mortality especially as we tend to see more advanced stages of breast cancer in our part of the world ( 2 , 3 ). (ispub.com)
  • The histological type of breast cancer comprised 137 infiltrating ductal carcinoma (not otherwise specified), 4 invasive lobular carcinoma, 3 papillary, 2 mucinous, one each of medullary, tubular and inflammatory carcinoma, 27 ductal carcinoma in situ and 1 Non Hodgkin lymphoma. (ispub.com)
  • SERMs block estrogen receptors within breast cells, thereby reducing estrogen-stimulated growth. (texasoncology.com)
  • While many factors are involved in the etiology of cancer, it has been clearly established that diet significantly impacts risk of this disease [ 1 , 2 , 3 ]. (mdpi.com)