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  • Antibody
  • The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-ErbB2 antibody linked to CD28 and CD3ζ signaling domains. (creative-biolabs.com)
  • Store at 2 to 8 degree C. Antibody is stable for 24 months. (mybiosource.com)
  • Small volumes of anti-ERBB2 antibody vial(s) may occasionally become entrapped in the seal of the product vial during shipment and storage. (mybiosource.com)
  • 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)
  • To understand the correlation between HER-2/neu expression and TNF resistance, we examined the unique signaling pathways associated with the cytotoxic effects of the immunocytokine scFv23/TNF, recombinant single-chain antibody fusion constructs containing TNF and targeting HER-2/neu, in TNF-resistant SKBR-3-LP cells. (aacrjournals.org)
  • With the use of an antibody construct containing TNF, we initially showed that delivery of TNF to tumor cells, using first chemical conjugates and then recombinant single-chain antibody fusion constructs containing TNF and targeting gp240 (ZME/TNF) and HER-2/neu (scFv23/TNF), could overcome resistance of tumor cells to TNF in vitro ( 18 , 21 , 22 ). (aacrjournals.org)
  • The following antibody was used in this experiment: Phospho-ErbB2 (HER-2) (Tyr1248) Monoclonal Antibody (PN2A) from Thermo Fisher Scientific, catalog # MA5-11367, RRID AB_10980292. (thermofisher.com)
  • The following antibody was used in this experiment: ErbB2 (HER-2) Monoclonal Antibody (N24) from Thermo Fisher Scientific, catalog # MA1-12691, RRID AB_1073577. (thermofisher.com)
  • We have downregulated cell surface expression of individual erbB receptors via intracellular antibody expression prior to analyzing ligand induced signaling. (springer.com)
  • The following antibody was used in this experiment: ErbB2 Monoclonal Antibody (2G11), Biotin from Thermo Fisher Scientific, catalog # AHO0919, RRID AB_2536319. (thermofisher.com)
  • More attention is being paid to HER-2 and its role in breast cancer because of the recent introduction of trastuzumab, a humanized murine monoclonal antibody directed against the extracellular domain of HER-2, for the treatment of patients with HER-2-overexpressing advanced breast cancer ( 6 , 7 ). (aacrjournals.org)
  • We used two independent methods, expression of intracellular single-chain antibody against HER-2 and treatment with a novel dual EGFR/HER-2 kinase inhibitor GW572016 (lapatinib). (aacrjournals.org)
  • Expression of intracellular HER-2 antibody scFv-5R and treatment with GW572016 inhibited HER-2 signaling. (aacrjournals.org)
  • Inactivation of AR by antibody, ribozyme, or RNA interference results in inhibition of proliferation or tumorigenicity of hormone refractory prostate cancer cells ( 1 , 2 ). (aacrjournals.org)
  • Therefore, in this study, we investigated the effect of inhibiting HER-2 using an intracellular antibody and a novel kinase inhibitor GW572016. (aacrjournals.org)
  • tumor
  • Together, our findings indicate that nuclear ErbB2 functions as a regulator of rRNA synthesis and cellular translation, which may contribute to tumor development and progression. (aacrjournals.org)
  • The expression of both genes is associated with tumor aggressiveness and is related to a lower response to treatment. (aacrjournals.org)
  • The high levels of the erbB-2 product associated with malignant transformation of NIH/3T3 cells were observed in human mammary tumor cells that overexpressed this gene 3 . (apexbt.com)
  • Tid1, the human homologue of a Drosophila tumor suppressor, reduces the malignant activity of ErbB-2 in carcinoma cells. (nih.gov)
  • We discovered that this domain of ErbB-2 interacts with Tid1 protein, the human counterpart of the Drosophila tumor suppressor Tid56, whose null mutation causes lethal tumorigenesis during the larval stage. (nih.gov)
  • Importantly, ErbB-2-dependent tumor progression in animals is inhibited by increased expression of Tid1 in tumor cells. (nih.gov)
  • Collectively, these results suggest that Tid1 modulates the uncontrolled proliferation of ErbB-2-overexpressing carcinoma cells by reducing ErbB-2 expression and as a result suppresses the ErbB-2-dependent cancerous signaling and tumor progression. (nih.gov)
  • We also compared age at diagnosis and tumor histologic grade with IHC and CISH Her-2/ neu . (biomedcentral.com)
  • Her-2/ neu testing should be done on all breast cancer cases regardless of age at presentation and tumor histologic grade. (biomedcentral.com)
  • The use of antibodies for the specific delivery of cytokines to tumor cells has been shown by numerous groups using TNF, IFN, interleukin 2, and lymphotoxin ( 18 - 20 ). (aacrjournals.org)
  • Down-regulation of ErbB2 and inhibition of HAEC growth by cocoa procyanidins may have several downstream implications, including reduced vascular endothelial growth factor (VEGF) activity and angiogenic activity associated with tumor pathology. (biomedsearch.com)
  • To experimentally address the potential involvement of AP-2 in mammary gland tumorigenesis, we generated mice overexpressing AP-2γ by transgenesis using the mouse mammary tumor virus-long terminal repeat as the transgene-driving promoter unit. (aacrjournals.org)
  • Research studies have demonstrated that in tumor development, ErbB3 may function as an oncogenic unit together with other ErbB members (e.g. (cellsignal.com)
  • ErbB2 requires ErbB3 to drive breast tumor cell proliferation) (7). (cellsignal.com)
  • Thus, investigators view inhibiting interaction between ErbB3 and ErbB tyrosine kinases as a novel strategy for anti-tumor therapy. (cellsignal.com)
  • The gene expression signature revealed various genes previously described to be associated with breast cancer, such as the activator protein-1 complex member Fos-like antigen 2 ( Fosl2 ), early growth response 1 ( Egr1 ), gelsolin ( Gsn ), and tumor protein translationally controlled 1 ( Tpt1 ), among others. (aacrjournals.org)
  • Human breast cancer therapeutic and preventive agents are primarily grouped based on their mechanism of action about the estrogen receptor-α status of the tumor. (aacrjournals.org)
  • Our results suggest that the currently identified genetic polymorphisms of HER-2 are not associated with an increased risk of breast cancer in Korean women, whereas one haplotype does affect protein expression of the tumor and disease outcome. (aacrjournals.org)
  • antigen
  • Immunohistological examination revealed the presence of enterovirus in pancreatic islet cells and exocrine tissues and hyperexpression of pattern recognition receptors (PRRs) including melanoma differentiation-associated antigen 5 (MDA5), retinoic acid-inducible gene-I (RIG-I), Toll-like receptor (TLR)3 and TLR4, essential sensors of innate immunity, in islet cells and mononuclear cells (MNCs) infiltrating islets. (cancerindex.org)
  • CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins which are expressed on antigen-presenting cells (APC). (creative-biolabs.com)
  • This HER-2 inhibition led to impairment of AR-mediated functions, such as androgen-stimulated growth and the induction of endogenous prostate-specific antigen (PSA) mRNA and protein. (aacrjournals.org)
  • metastatic
  • As demonstrated by clinical trials (14) , these antibodies are well tolerated and clinically active in patients with metastatic breast cancer overexpressing c-erbB-2 and result in an increase in the objective clinical response rates when used in combination with chemotherapy. (aacrjournals.org)
  • Immunohistochemistry
  • Chromogenic in situ hybridization (CISH) is emerging as a practical, cost-effective, and valid alternative to fluorescent in situ hybridization in testing for gene alteration, especially in centers primarily working with immunohistochemistry (IHC). (biomedcentral.com)
  • ER, PR, and c-erbB2 levels in the breast tissue samples were evaluated using immunohistochemistry (IHC) after the frozen and regular follow-up methods. (turkjsurg.com)
  • Expression of HER-2 protein was determined by immunohistochemistry in 1,094 cases of invasive breast cancer. (aacrjournals.org)
  • ligand
  • Finally, ErbB2-potentiated RNA Pol I transcription could be stimulated by ligand and was not substantially repressed by inhibition of PI3-K and MEK/ERK (extracellular signal regulated kinase), the main ErbB2 effector signaling pathways. (aacrjournals.org)
  • 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. (creative-biolabs.com)
  • Receptors of this family are located on the plasma membrane and consist of an extracellular ligand-binding domain that is connected to a large intracellular domain by a single transmembrane sequence. (mybiosource.com)
  • Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. (abcam.com)
  • GP30 is a potential ligand for this receptor. (abcam.com)
  • Upon ligand binding, heterodimers form between ErbB3 and other ErbB proteins, and ErbB3 is phosphorylated on tyrosine residues by the activated ErbB kinase (1,2). (cellsignal.com)
  • scFv
  • The ready-to-use lentiviral particles of Lenti-ErbB2 CAR (scFv-28ζ, C6ML3-9)-VP is packaged using 3rd generation of lentiviral packaging system, in which the gene of CAR will be driven by a CMV promotor. (creative-biolabs.com)
  • The target gene of scFv (C6ML3-9)-CD28-CD3ζ packaged in lentiviral particles could be used for high efficency tranduction of T cells and stably integrated expression. (creative-biolabs.com)
  • Intracellular expression of an scFv that competes with EGF was found to inhibit EGF receptor function in an autocrine manner. (springer.com)
  • In NIH/3T3 fibroblasts transformed by a mutated, constitutively active erbB-2, scFv-mediated intracellular retention of erbB-2 led to complete reversion of the transformed phenotype. (springer.com)
  • Regulation
  • Although it has been known that nuclear RTKs associate with functions in RNA Pol II transcriptional regulation, DNA repair, and DNA replication ( 12-16 , 20 , 26-32 ), the biological significance and functions of the nuclear RTKs, including ErbB2, is still far from clear. (aacrjournals.org)
  • Unlike other members of the family, the protein encoded by this gene does not directly control cell cycle regulation. (cancerindex.org)
  • We report that the pentameric procyanidin (molecular weight of 1442 daltons) fraction isolated from cocoa was a potent inhibitor of tyrosine kinase ErbB2 expression, a receptor important in angiogenesis regulation. (biomedsearch.com)
  • Semaphorin/plexin signalling results in activation of receptor tyrosine kinases and modulation of the actin cytoskeleton via regulation of several specific small RhoGTPases. (biomedcentral.com)
  • AP-2 proteins have been implicated in the regulation of cell type-specific processes based on their expression in neural, neural crest, kidney, and epithelial cells during development. (aacrjournals.org)
  • ErbB2 is a key therapeutic target in the treatment of breast cancer and other carcinomas and targeting the regulation of ErbB2 degradation by the c-Cbl-regulated proteolytic pathway is one potential therapeutic strategy. (cellsignal.com)
  • RTKs
  • Key molecules of these pathways are the receptor tyrosine kinases (RTKs), which are found to be aberrantly activated or overexpressed in a variety of tumours and therefore represent promising targets for therapeutical intervention. (biomedcentral.com)
  • In addition to traditional signaling pathways, compelling evidence shows that RTKs, comprising ErbB family, are present in the nucleus ( 12-17 ). (aacrjournals.org)
  • Proteins
  • The AP-2 family of transcription factors consists of four homologous proteins of M r 50,000, AP-2α, AP-2β, AP-2γ, and AP-2δ ( 1 ), encoded by different genes (reviewed in Ref. 2 ). (aacrjournals.org)
  • The expression of AP-2 proteins has been associated with neoplasia of the breast, a process where the normal growth and differentiation program of epithelial cells is disturbed ( 10 ). (aacrjournals.org)
  • moreover, the erbB-2 promoter was shown to contain an AP-2 binding site and could be transactivated by AP-2 proteins in cell transfection studies ( 13 ). (aacrjournals.org)
  • These sites serve as consensus binding sites for signal transducing proteins, including Src family members, Grb2, and the p85 subunit of PI3 kinase, which mediate ErbB downstream signaling (3). (cellsignal.com)
  • The 5' flanking region contains several consensus binding sites for transcription factors that regulate gene expression during tissue and organ development, such as myeloid zinc finger ( MZF1 ), Ikaros 2 and homeodomain proteins, as well as factors implicated in cell growth and survival responses, including AP-1 , PEA3 , E2F and NF-kB . (atlasgeneticsoncology.org)
  • downstream
  • Conclusions- These data suggest that deregulation of FOXC1 or its downstream genes play a major role in the pathogenesis of coarctation of the aorta in humans. (ahajournals.org)
  • inhibition
  • A functional DnaJ domain of Tid1 also is required for its inhibition of ErbB-2 expression and the consequent PCD of carcinoma cells resulting from increased Tid1 expression. (nih.gov)
  • Androgen-stimulated recruitment of AR and histone acetylation at the androgen responsive enhancer of the PSA gene, detected by chromatin immunoprecipitation analysis, were impaired by HER-2 inhibition. (aacrjournals.org)
  • These results show that HER-2 signaling is required for optimal transcriptional activity of AR in prostate cancer cells and suggest that HER-2 inhibition may provide a novel strategy to disrupt AR function in prostate cancer. (aacrjournals.org)
  • Our results show that HER-2 inhibition leads to impairment of AR transcriptional function at the level of recruitment of AR to the androgen responsive enhancer on chromatin. (aacrjournals.org)
  • transcription
  • In this study, we defined a novel function of nuclear ErbB2 in enhancing rRNA gene transcription by RNA polymerase-I (RNA Pol I). Nuclear ErbB2 physically associates with β-actin and RNA Pol I, coinciding with active RNA Pol I transcription sites in nucleoli. (aacrjournals.org)
  • A search for transcription factor binding sites showed that 93% of the rare CNVs identified in patients with coarctation of the aorta contained at least 1 gene with FOXC1-binding sites. (ahajournals.org)
  • Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. (abcam.com)
  • Our results suggest a role of AP-2 transcription factors in the maintenance of a proliferative and undifferentiated state of cells, characteristics not only important during embryonic development but also in tumorigenesis. (aacrjournals.org)
  • These transcription factors homo- or heterodimerize via helix-span-helix motifs and transactivate their target genes by binding to GC-rich consensus sequences in the respective promoter regions ( 3 , 4 ). (aacrjournals.org)