Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The HER-2/neu oncogene (a member of the Erb-like oncogene family) is distinct from but closely related to the c-erb B gene which encodes the epidermal growth factor receptor (EGFr). HER-2/neu gene amplification was found in a large number of mammary carcinomas and there was a strong correlation between this phenomenon and poor prognosis. In our study HER-2/neu oncogene expression was determined in 16 malignant ovarian tumors, 2 ovarian lymphomas and 5 normal ovaries. The HER-2/neu gene was found both in normal ovaries and malignant tumors, without any apparent difference among the various histological types. In all the specimens examined, HER-2/neu expression did not seem to be related to EGF binding capacity.
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PMID:Preliminary evaluation of HER-2/neu oncogene and epidermal growth factor receptor expression in normal and neoplastic human ovaries. 163 22

In 43 cases of adenoid cystic carcinomas of the salivary glands (ACC), expressions of the oncogene products such as epidermal growth factor receptor (EGF-R), erbB-2 product, c-myc product and N-myc product were investigated immunohistochemically. First, we confirmed the specificity of the antibodies used with the 13 cell lines. Of the anti-EGF-R antibodies, clone 29. 1. 1 reacted only with A431 but not with the other cell lines overexpressing EGF-R, so that it was most likely to cross-react with the blood type A antigen. Also, the anti-N-myc product antibody revealed the presence of a certain cross-reacting antigen in Lu65. Overexpression of EGF-R was observed in only one case. Nine cases (20.9%) showing tubular and cribriform patterns overexpressed the erbB-2 product, but the signals were mainly localized in the cytoplasm as a granular appearance. Eighteen cases (41.9%) with slight cellular atypia showed an overexpression of the c-myc product. The immunolocalization of the c-myc product was at the nuclei in most cases, or both the nuclei and the cytoplasm in some cases. None of the ACC expressed the N-myc product. It is speculated that the multiple oncogene expressions might be partly related to the acquirement of the differentiated or malignant phenotype in the ACC.
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PMID:[Expressions of oncogene products in adenoid cystic carcinomas of salivary glands: immunohistochemical study]. 166 2

The expression of the EGF receptor, c-erbB-2 and PDGF receptor proteins has been studied in a series of human brain tumour biopsies and cell lines. Western blotting was used to determine the amount of protein present and their intrinsic and ligand promoted enzyme activities were studied by immunoprecipitation followed by autophosphorylation. EGF receptors were found to be expressed at very high levels in 40% of primary tumour biopsies, but at uniformly low levels in tumour derived cell lines. The c-erbB-2 protein was not detected in tumour biopsies, but was present at variable, but low levels in extracts of tumour cell lines. PDGF receptors were also found at moderate to low levels in both primary tumours and cell lines. The EGF receptor gene was amplified in four out of 14 primary tumours and this generally correlated with high levels of protein expression. The c-erbB-2 gene was not amplified. Employing the polymerase chain reaction and sequence specific oligonucleotides as probes there was no evidence of mutations in the c-erbB-2 gene transmembrane region. These results suggest that alterations of expression of the EGF receptor may play a role in human brain tumours. There was however no evidence for aberrant expression of the c-erbB-2 protein. Additional experiments are required to assess the influence of PDGF receptor expression in brain tumour cells.
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PMID:Expression of growth factor receptors in human brain tumours. 167 51

A retroviral expression vector carrying the c-erbB-2 gene was introduced into the FDC-P2 myeloid cell line, which is absolutely dependent on interleukin-3 (IL-3) for proliferation and survival. Since the c-erbB-2 protein appears to be the receptor of an as yet unidentified growth factor, epidermal growth factor receptor (EGFR) was used as a control of a ligand-dependent receptor. FDC-P2 cells expressing normal c-erbB-2 were unable to grow without IL-3 stimulation. The c-erbB-2 protein in these cells was under-phosphorylated on tyrosine residues in vivo. On the contrary, the active c-erbB-2 protein, in which Val-659 was replaced by Glu in the transmembrane domain, and EGF-stimulated EGFR showed significant levels of tyrosine phosphorylation in vivo. These active proteins could promote short-term growth of FDC-P2 cells without IL-3 stimulation, though not indefinitely. These findings suggested that immortalization of this factor-dependent cell line requires an additional oncogenic promoting process(es).
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PMID:Active c-erbB-2 induces short-term growth of FDC-P2 cells after IL-3 depletion. 168 97

Monoclonal antibodies to myc, c-erbB-2 and epidermal growth factor-receptor (EGF-R) were raised using a synthetic peptide approach. The antibodies were characterised by ELISA, immunoblotting, immunoprecipitation and immunocytochemical procedures against cognate peptide and native proteins. All of the monoclonal antibodies detected peptide-blockable bands of appropriate molecular weight (myc-p62/66 kDa, c-erbB-2-185kDa; EGF-R-150/170 kDa) on immunoblots. The monoclonal antibodies to c-erbB-2 and EGF-R immunostained subpopulations of tumour cells on sections of formalin-fixed, paraffin wax embedded human infiltrating and invasive ductal carcinomas of breast. Intense blood cell staining was observed with the EGF-R antibody. This staining was shown to be peptide blockable and may reveal a true localisation for the EGF-receptor protein, a closely-related (erbB) protein or a degradation product. The monoclonal antibody to a common peptide from the myc protein family was epitope scanned using a modification of the Geysen pin technique. Hexapeptide sequence Ala-Pro-Ser-Glu-Asp-Ile was found to be bound most strongly by the myc monoclonal antibody, and amino acids Pro2 and Glu4 were found to be essential for antibody binding. The use of synthetic peptides for the production of monoclonal antibodies with predetermined specificity, which may be precisely identified using the epitope scanning technique, is discussed.
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PMID:The production and characterisation of monoclonal antibodies to myc, c-erbB-2 and EFG-receptor using a synthetic peptide approach. 169 66

The effect of tyrosine kinase inhibitor, erbstatin, on cell growth and mRNA expression of growth-factor/receptor system was examined in 6 human gastric-carcinoma cell lines. Erbstatin inhibited both EGF-induced and serum-stimulated cell growth of all 6 cell lines (TMK-1, MKN-1, -7, -28, -45, -74) in a dose-dependent manner. 3H-thymidine incorporation by TMK-1 cells was also suppressed by erbstatin. Erbstatin inhibited protein kinase activity of EGF receptor, p185ERBB2 and pp60c-src in TMK-1 cells. The expression of mRNA of EGF receptor gene and ERBB-2 by TMK-1 cells was not changed by erbstatin treatment, whereas that of c-src was slightly decreased. Interestingly, erbstatin decreased membrane-bound TGF-alpha precursor as measured by anti-TGF-alpha antibody-binding assay, although mRNA expression for TGF-alpha was not altered by erbstatin. Our findings suggest that erbstatin may act as a growth inhibitor for human gastric-carcinoma cells and may not only inhibit tyrosine kinase activities but also negatively modulate the post-transcriptional step of TGF-alpha expression.
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PMID:Effects of tyrosine kinase inhibitor, erbstatin, on cell growth and growth-factor/receptor gene expression in human gastric carcinoma cells. 184 25

The C-erbB-2 gene was first found in human genomic DNA as a sequence which had homology in nucleotide sequence to the V-erbB by molecular hybridization under relaxed conditions. The product of this gene is a receptor type protein-tyrosine kinase which has a structure highly related to that of epidermal growth factor receptor (EGF-r: C-erbB-1). The proto-neu gene is a rat counterpart of the C-erb B-2 gene. The C-erbB-2 gene is also called as the HER-2 gene. The C-erbB-2 gene acquires the ability to transform NIH 3 T 3 cells by, 1) mutation which alters valine 659 in transmembrane region to glutamic acid as was found in neu gene activation, 2) deletion of c-terminal regulatory domain or 3) gene-amplification or overexpression. C-erbB-2 expresses in human embryos on mucous membranes and glands, but only faintly in adult tissues. High expression or gene amplification in human tumor appeared to be an indication for high risk of metastasis or high degree of malignancy.
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PMID:[Proto-oncogene C-erbB-2 and human cancer]. 196 37

Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis. For detection of the c-erbB-2 product, two specific antibodies, a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain, were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2 polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with good correlation on both stainings (p less than 0.01). There were four c-erbB-2 positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors. There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine of 45 superficial tumors, four of five with lymph node metastasis, and seven of 14 without metastasis, as revealed by staining with the polyclonal antibody. Thus, the c-erbB-2 gene product was more frequently expressed in high grade tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R was independent of histological grading, tumor stage, and nodal status, and no correlation was observed between expression of the c-erbB-2 product and EGF-R. The c-erbB-2 product may be applicable as a tumor marker for evaluation of malignant potential, invasiveness, and probably metastatic potential of human bladder cancer.
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PMID:Expression of c-erbB-2 gene product in urinary bladder cancer. 198 41

The development of human lung cancer may require multiple genetic deletions affecting a number of chromosomes, e.g., 1, 3, 11, 13, and 17. These genetic aberrations may induce the activation of proto-oncogenes (c-jun, ras, c-raf1) and the loss of tumor suppressor genes (p53). Some of the activated proto-oncogenes and tumor suppressor genes are more selectively expressed or absent in small-cell lung cancer (L-myc, c-myb, c-scr, Rb gene) or non-small-cell lung cancer (c-erbB-2, c-sis, c-fes). These genes may thus be of importance for selection of differentiation pathway. The c-myc oncogene is frequently amplified in small-cell lung cancer cell lines in a much higher frequency than in vivo. This indicates that c-myc seems to be related to tumor progression and a relatively late event in the lung cancer development. The uncontrolled production of multiple growth factors has been identified in human lung cancer cell lines. These factors can promote and inhibit the proliferation via paracrine and autocrine loops via specific receptors. The products from some of the activated proto-oncogenes (c-sis, c-erbB-2) are sequences homologous to a certain growth factor (PDGF) and a receptor (EGF) identified in lung cancer. The production and action of these growth factors may be of major importance for further activation of proto-oncogenes via intracellular signal transduction and specific oncogenic activation leading to further tumor progression.
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PMID:Gene amplification in human lung cancer. The myc family genes and other proto-oncogenes and growth factor genes. 217 59

Expression of the product of the c-erbB-2 gene, a proto-oncogene related to, but distinct from c-erbB-1 encoding the epidermal growth factor receptor (EGF-R), was investigated in human urinary bladder carcinomas. In addition, levels of EGF-R and transferrin receptor were also analyzed using an immunohistochemical approach, and the results compared with histological pattern and grading, and tumor staging. Increased expression of c-erb B-2 product was found in 32% of cases (7/22), a positive reaction being observed in 60% of transitional cell carcinoma (TCC) Grade 3 lesions (3/5), 20% of Grade 2 TCCs (2/10) and 100% of adenocarcinomas (AC) (2/2), but in none of the cases of squamous cell carcinoma (SCC). Although no statistical correlation with staging was evident, TCCs or SCCs of high grade and stage often showed EGF-R-positive staining, whereas other well differentiated lesions and normal bladder epithelium were generally negative. Most cases of urinary bladder carcinoma were positive for the transferrin receptor, which was not detected in normal bladder. The results thus suggested that a positive reaction for c-erbB-2 product is correlated with TCC histological grading or AC morphology. A high intensity of EGF-R staining in human bladder carcinomas may be associated with poor differentiation and invasion, whereas transferrin receptor expression might reflect tumor growth.
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PMID:Immunohistochemical analysis of c-erbB-2 oncogene product and epidermal growth factor receptor expression in human urinary bladder carcinomas. 220 26


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