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)

BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian cancer syndrome. To clarify the possible involvement of the BRCA1 protein in mammary carcinogenesis in sporadic and hereditary forms, we have analyzed the BRCA1 protein expression pattern in five breast epithelial cell lines, including a BRCA1-deficient cell line, and 162 breast cancer tissue samples [including 108 sporadic, 35 hereditary (BRCA1 status unknown), and 19 BRCA1-associated cases] from Japanese women. Twelve anti-BRCA1 antibodies were tested by fixation conditions, in which nuclear localization of BRCA1 protein was preserved, and by specificity of the antibodies, which was evaluated in BRCA1-deficient cancer cells. Using monoclonal antibodies applicable to immunohistochemical analysis of paraffin-embedded tissue sections, we found high-level expression of BRCA1 protein in normal mammary epithelium and various degrees of reduced expression in breast cancer cells. Of the 19 BRCA1-associated breast cancer tissues, 15 (79%) showed reduction (8 cases) or complete loss (7 cases) of nuclear expression. Thirty (28%) of 108 sporadic and 6 (17%) of 35 hereditary carcinomas showed reduced BRCA1 protein expression. Reduction of BRCA1 protein expression in sporadic carcinomas was associated with solid-tubular phenotype, with poor tubular differentiation, and with an overexpression of c-erbB-2 protein, which is one of the prognostic factors in breast cancer. Our data suggest that reduced expression of BRCA1 protein may play an important role in mammary carcinogenesis, not only in BRCA1-associated breast carcinomas, but also in sporadic carcinomas, and also suggest that mechanisms other than mutation may be involved in its reduced expression.
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PMID:Reduction of BRCA1 protein expression in Japanese sporadic breast carcinomas and its frequent loss in BRCA1-associated cases. 1038 7

Young age does not seem to be directly related to the aggressiveness of the disease among patients with breast cancer. Identification and analysis of the alterations in a susceptibility gene expression in breast cancer occurring in young women may allow identification of those patients in whom tumors will show an aggressive clinical course. The purpose of the present study was to evaluate the association of BRCA1, H-ras, and c-erbB-2 gene expression with clinicopathologic parameters of prognosis in breast cancer. Formalin-fixed, paraffin-embedded tissue from 35 patients with breast cancer younger than 35 years were immunohistochemically stained for BRCA1, H-ras, and c-erbB-2 expression with monoclonal antibodies. For each antibody, immunoreactivity was assessed by a semiquantitative scoring system. Each case was also graded according to the modified Bloom-Richardson criteria and evaluated for Ki-67 labeling index, hormonal status, tumor size, distant metastasis, and axillary lymph node involvement. Strong expression of c-erbB-2 and H-ras were observed in 9 cases (25.7%) and 13 cases (37.2%), respectively. Loss of BRCA1 expression was found in five cases (14.3%). Statistical analysis showed that loss of BRCA1 expression was significantly associated with higher Ki-67 labeling index and greater tumor size. In addition, stronger H-ras expression was significantly associated with lymph node involvement and distant metastasis. However, c-erbB-2 immunoreactivity did not show statistical significance with any prognostic parameters. We conclude that, although care must be taken not to overstate the importance of our results in view of the lack of information on clinical outcome, alterations in BRCA1 and H-ras gene expression might be of prognostic importance because of the role of H-ras protein on metastatic behavior and the role of BRCA1 protein on tumor growth. However, c-erbB-2 expression seems to be of no importance in the prognosis of breast cancer occurring in young women.
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PMID:BRCA1, C-erbB-2, and H-ras gene expressions in young women with breast cancer. An immunohistochemical study. 1093 43

To test the hypothesis that altered expression of BRCA1 protein may play an important role in sporadic breast cancer development, 50 randomly selected primary breast cancers (frozen sections, 5 years' median follow-up) were immunolabelled with two monoclonal BRCA1 antibodies (MS110 and MS13). MS110 labelling was exclusively nuclear showing no relation to outcome or tumour pathology. Western blotting demonstrated crossreactivity, suggesting antibody nonspecificity. MS13 labelling was predominantly cytoplasmic. Intense labelling predicted decreased overall survival (P=0.012), disease-free survival (P=0.029), oestrogen receptor negativity (P=0.0004) and c-erbB-2 overexpression (P=0.006). Western blotting detected a 110 kDa molecule consistent with BRCA1 delta11b splice variant. BRCA1 protein is postulated to function as a tumour suppressor. We demonstrate cytoplasmic localisation in sporadic breast cancer suggesting excess delta11b splice variant production, reduced production of full-length BRCA1 and thus postulate reduced tumour suppressor activity. BRCA1 protein appears to have a significant role in both sporadic and hereditary breast cancers.
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PMID:A role for BRCA1 in sporadic breast cancer. 1269 94