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)

Purified preparations of epidermal growth factor (EGF) receptor were used to test hen oviduct progesterone receptor subunits as substrates for phosphorylation catalyzed by EGF receptor. Both the 80-kilodalton (kDa) (A) and the 105-kDa (B) progesterone receptor subunits were phosphorylated in a reaction that required EGF and EGF receptor. No phosphorylation of progesterone receptor subunits was observed in the absence of EGF receptor, even when Ca2+ was substituted for Mg2+ and Mn2+. Phospho amino acid analysis revealed phosphorylation at tyrosine residues, with no phosphorylation detectable at serine or threonine residues. Two-dimensional maps of phosphopeptides generated from phosphorylated 80- or 105-kDa subunits by tryptic digestion revealed similar patterns, with resolution of two major, several minor, and a number of very minor phosphopeptides. The Km of progesterone receptor for phosphorylation by EGF-activated EGF receptor was 100 nM and the Vmax was 2.5 nmol/min per mg of EGF receptor protein at 0 degrees C. The stoichiometry of phosphorylation/hormone binding for progesterone receptor subunits was 0.31 at ice-bath temperature and approximately 1.0 at 22 degrees C.
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PMID:Progesterone receptor subunits are high-affinity substrates for phosphorylation by epidermal growth factor receptor. 620 Aug 81

Antagonists of steroid hormones are clinically important in the management of breast cancer. However, the duration of response is limited due to the development of hormone-independent tumors in virtually all cases. In an attempt to obtain insight into the mechanisms underlying antiestrogen resistance, the consequences of epigenetic changes in gene expression were studied in vitro. Estrogen-dependent ZR-75-1 human breast cancer cells were treated with 5-azacytidine, an inhibitor of DNA methylation, and cultured in the absence of estradiol or in the presence of antiestrogens. Estrogen-independent cell colonies developed within 3 weeks at high frequency in 5-azacytidine-treated cultures (0.7 x 10(-3), in contrast to control cultures (< or = 10(-8). The derived cells (ZR/AZA) were resistant to 4-hydroxytamoxifen and ICI 164,384, independent of the selection protocol, but had lost the ability to grow anchorage-independent. Whereas expression of estrogen receptor, progesterone receptor, and pS2 were down-regulated, expression of epidermal growth factor (EGF) receptor and HER2/neu were increased in ZR/AZA cells. In contrast to the stable altered expression patterns of estrogen receptor and EGF receptor, transient keratin 7 expression was observed. Transforming growth factor-alpha mRNA was identified in ZR-75-1 cells and ZR/AZA cells and EGF-like peptides were secreted in the culture medium. Proliferation of ZR/AZA cells could be partially inhibited with an EGF receptor-blocking antibody. Presence of both growth factor receptors and possible ligands suggests the development of an autocrine growth mechanism. Our data show that epigenetic alterations of gene expression result in rapid progression of breast cancer cells to hormone independence.
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PMID:Induction of estrogen independence of ZR-75-1 human breast cancer cells by epigenetic alterations. 753 60

Using a commercial kit with antibodies against the ectodomain of c-erbB-2 protein, we detected c-erbB-2 immunoreactivity in human serum. We found that the percentages of patients with elevated serum c-erbB-2 immunoreactivities were 35, 21, and 9% in breast, prostate, and ovarian carcinoma, respectively. The majority of the elevated immunoreactivities were associated with sera containing highly elevated tumor markers with the highest in breast carcinoma (35%) and lowest in ovarian cancer (9%). Excellent correlations were also observed between the serum levels of c-erbB-2 immunoreactivity and the dominant tumor markers in serial specimens from individual cancer patients. We could also detect the c-erbB-2 immunoreactivity in the cytosols prepared from the breast tumor tissue for estrogen and progesterone receptor (ER & PgR) measurements using the same commercial kit for serum studies, and the intact c-erbB-2 oncoprotein (p185) in the extracts of the tissue membrane fractions with a different kit designed for tissue extract. The level of c-erbB-2 immunoreactivity in the cytosol from 124 human breast tumor specimens had an excellent correlation with the cell membrane concentrations of p185 (gamma = 0.89). Most of the elevated cytosol c-erbB-2 immunoreactivities were also found to associate with breast tumor specimens containing low concentrations of ER & PgR. It appears that measuring the c-erbB-2 immunoreactivity potentially could be used as a prognostic marker without performing tissue biopsies and also as a serum tumor marker for managing cancer patients.
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PMID:Measurement of c-erbB-2 proteins in sera from patients with carcinomas and in breast tumor tissue cytosols: correlation with serum tumor markers and membrane-bound oncoprotein. 754 55

We have determined the average gene copy numbers (AGCN) of the erbB-1 gene, encoding the epidermal growth factor receptor (EGF-R), the erbB-2 and the erbB-3 genes in breast, ovarian, oral, and lung cancer tissue by using double-differential PCR (ddPCR). The ddPCR method comprises the co-amplification of the single-copy gene HBB, the erbB-1, erbB-2 and erbB-3 oncogenes and the second single-copy reference gene SOD2 under equal reaction conditions. In a retrospective study the AGCN of the erbB genes and the time up to the appearance of metastases were subjected to life-table analysis in 128 women with primary breast cancer. Patients whose breast cancer tissue showed an AGCN for erbB-1 of less than 0.4 and greater then 1.6, as expected from the literature, for erbB-2 of greater than 2.0 and for erbB-3 of less than 1.75 had decreased disease-free survival (DFS). The quotient of erbB-1 and erbB-2 AGCN was the most significant in multivariate Cox analysis followed by nodal status and progesterone receptor status. In extensive studies a similar association between erbB AGCN and metastasis was seen in ovarian cancer and oral cancer, though erbB oncogene aberrations in those entities were not as frequent as in breast cancer. The AGCN of erbB oncogenes may not be of prognostic value in untreated lung cancer patients.
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PMID:Prognostic relevance of aberrations in the erbB oncogenes from breast, ovarian, oral and lung cancers: double-differential polymerase chain reaction (ddPCR) for clinical diagnosis. 760 71

The concentration of c-erbB-2 oncoprotein (HER-2/neu) was examined in the membrane fraction of 196 breast cancer and 39 benign breast specimens using a recently introduced ELISA-assay. The results were compared with established clinical and laboratory prognostic factors, 19% of all breast cancer specimens showed a c-erbB-2 protein level above 10 HNU/micrograms extract protein and were so classified as positive. Considering only the samples of primary tumors the rate was 21%. Surprisingly the rate was only 13.5% in the tissue samples of recurrent disease. Significant correlations were found between high c-erbB-2 protein levels and the tumor diameter, the axillary lymph node status and the progesterone receptor status. In contrast no correlation was found with estrogen receptor or menopausal status. All specimens of benign tumors showed levels < 10 HNU/micrograms extract protein and were classified as negative. The measurement of the c-erbB-2 protein using this ELISA assay was simple to perform and revealed reliable results. Nevertheless the prognostic power of the c-erbB-2 protein seems to be of minor relevance in comparison with established clinical and laboratory parameters, as the positive rates are too small in regard to the much higher recurrence rates of breast cancer. Probably the serum levels of this oncoprotein will be of greater clinical interest in the course of breast cancer.
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PMID:Level of c-erbB-2 oncoprotein in the homogenate of malignant and benign breast tumor samples. 764 40

Amplification of HER-2(erbB-2/neu) oncogene was detected in 36 of 142 (25%) breast carcinomas (BC) RNA expression was examined in 42 carcinomas, in 10 of them overexpression was revealed. Amplification was matched by overexpression. No association was found between the increased number of HER-2(erbB-2/neu) copies and tumor size, lymph node involvement, stage of disease, age of onset, and estrogen and progesterone receptor level. HER-2(erbB-2/neu) amplification was shown to be of independent prognostic significance in the group of 32 BC patients with sufficient follow-up (more than 40 months). Six of 7 HER-2(erbB-2/neu) amplification-positive patients and only 2 of 25 HER-2(erbB-2/neu) amplification-negative ones relapsed (p < 0.00005).
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PMID:Amplification of HER-2(erbB-2/neu) oncogene as the most significant prognostic factor in a group of Russian breast cancer patients. 768 67

The increasing use of neoadjuvant chemotherapy and endocrine therapy in the management of breast cancer has lead us to evaluate and optimise the standard technique of cytocentrifugation of a single fine needle aspirate (FNA) taken from a breast tumour in-vivo, to determine a range of both immunocytochemical and flow cytometric factors which are predictive of response to primary medical therapy. Some of these factors are also of prognostic significance in early stage disease. An analysis of the cellularity and immunocytochemical staining characteristics of FNAs obtained from a series of 206 patients with palpable breast cancers indicate that in a sample of 46 cases it is possible to measure oestrogen receptor, progesterone receptor and c-erbB-2 providing over 400 cells per slide are obtained, with material obtained in a single FNA prepared by cytocentrifugation, using standard immunocytochemical methods. The staining results obtained were comparable to those obtained using frozen or paraffin embedded tissue sections taken from the same tumour. In addition an estimate of the proliferation indices could be made by flow cytometric analysis of the residual cell suspension fluid with measurement of DNA index and S-phase fraction in 131/164 (80%) and 110/164 (67%) of cases respectively. Providing all FNAs obtained for cytocentrifugation were taken at first presentation rather than immediately following a standard FNA, then it was possible to obtain adequately cellular (> 400 cells/slide) samples in 96 out of 126 (75%) of the last cohort of breast aspirates. These effects may be independent of T stage but not histological type as patients with lobular tumours only produced cellular aspirates in 1/7 (14%) of cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Determining factors which predict response to primary medical therapy in breast cancer using a single fine needle aspirate with immunocytochemical staining and flow cytometry. 775 86

Breast carcinomas are known to express platelet-derived growth factor (PDGF), a known connective tissue mitogen. In order to further evaluate the potential role of PDGF in these epithelial tumors, expression of the PDGF B chain (PDGF-B) and the PDGF receptor beta subunit (PDGFR) was analyzed by immunocytochemistry and in situ hybridization in 49 benign and malignant breast tissues. PDGF-B expression was analyzed with respect to the expression of the proliferating cell nuclear antigen, as well as tumor grade, p53 overexpression, estrogen receptor, progesterone receptor, and c-erbB-2 expression. Expression of PDGF-B protein and mRNA was restricted to the breast epithelium and tumor cells except for scattered tissue macrophages. A strong correlation was found between increasing proliferating cell nuclear antigen indices and PDGF-B expression in both nonmalignant (P = 0.01) and malignant (P = 0.02) breast specimens. Decreased PDGF-B expression was found in postmenopausal atrophic breast tissue compared with normal breast tissue (P = 0.04). Within the subgroup of malignant tumors, no correlations were found between PDGF-B expression and tumor grade or p53 overexpression. In 16 of the malignant tumors evaluated for estrogen/progesterone receptor status and c-erbB-2 overexpression, no correlations with PDGF-B expression were found. Membranous PDGFR immunostaining was present within the fibroblastic cell population in all of the tissues examined but not in the nonmalignant breast epithelium. Six malignant specimens had detectable cytoplasmic expression of PDGFR. There was no correlation between this PDGFR expression and proliferating cell nuclear antigen indices, but a correlation was noted between increasing estrogen receptor expression and PDGFR cytoplasmic expression (P = 0.04). The results support a paracrine role for PDGF-B in malignant and benign breast epithelial cell proliferation.
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PMID:Expression of platelet-derived growth factor B-chain and the platelet-derived growth factor receptor beta subunit in human breast tissue and breast carcinoma. 778 Sep 88

The pathological and biological features of a consecutive series of impalpable invasive breast carcinoma, detected by mammography in the prevalent round of the breast screening programme, have been compared with a clinically presenting group of carcinomas in age-matched patients. There was a significantly higher prevalence of tubular carcinomas as well-differentiated infiltrating ductal carcinomas in the mammographically detected group, and a lower prevalence of poorly differentiated infiltrating ductal carcinomas. Lymph node metastasis was found in 6.5% of the impalpable group compared with 53% of the clinical group. The prevalence of oestrogen receptor was much higher in the impalpable group (96%) than in the control group (67%), although there were no significant differences for progesterone receptor. The prevalence of pS2 was also much higher in the impalpable group, as was cathepsin D. This finding is surprising in view of the reported relationship between cathepsin D and poorer survival. p53 and c-erb-2 proteins were detectable in fewer impalpable carcinomas. The mean MIBI (Ki-67) index was lower in the impalpable group (11.6) than in the clinical group (15.25). Within the mammographically detected group there was a significant difference in the MIBI index between tubular carcinomas and the different grades of infiltrating ductal carcinomas, with a wide range in each category but no association with size. The impalpable carcinomas detected by mammography differ from clinically presenting carcinomas in many ways, raising the question of whether a proportion or all would progress (dedifferentiate) with time.
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PMID:Pathological and biological features of mammographically detected invasive breast carcinomas. 759 62

An epithelial ovarian cancer cell line is established from a patient with recurrent familial ovarian cancer. Two of the patient's sisters and her mother have also had ovarian cancer. The histological resemblance of the cell line to the patient's Stage IV, Grade 3 papillary serous ovarian primary cancer is striking. The cell line does not secrete CA125 and is estrogen and progesterone receptor negative. Overexpression of the p53 tumor suppressor gene but not the HER-2/neu oncogene was detected by immunohistochemical analysis. An unusual chemosensitivity to cisplatin, doxorubicin, etoposide, and taxol is demonstrated, suggesting that a chemosensitivity mechanism might explain prolonged survival of some patients with familial ovarian cancers. This truly unique cell line should prove invaluable in the further evaluation of molecular genetic changes associated with familial ovarian cancers.
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PMID:Isolation and preliminary characterization of an ovarian carcinoma cell line from a patient with familial ovarian cancer. 782 46


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