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)

Seven of 10 murine monoclonal antibodies reactive with the extracellular domain of p185c-erbB-2 inhibited the anchorage independent growth of the SKBr3 breast cancer cell line that overexpressed p185c-erbB-2. Significant inhibition (56-72%) of diacylglycerol (DAG) levels (P < 0.0001) was observed with the 10 antibodies that inhibited SKBr3 growth (RC1, NB3, RC6, PB3, 741F8, DB5, ID5), whereas the 3 antibodies (TA1, 520C9, 454C11) that failed to inhibit SKBr3 growth also failed to affect DAG levels. Thus, DAG levels correlated with antibody-mediated growth regulation for each of the 10 monoclonal reagents. Antibody-induced inhibition of anchorage-independent growth of SKBr3 could be reversed by incubation with phorbol myristate acetate. The ID5 antibody inhibited growth of the SKBr3, SKOv3, and OVCA 432 tumor cell lines, but not of OVCA 420, OVCA 429, and OVCA 433. DAG levels were significantly decreased after ID5 treatment of the SKBr3 and SKOv3 cell lines, but not the OVCA 420, OVCA 429, and OVCA 433 lines. In the 432 line, there was a decrease which did not reach significance. Consequently, changes in DAG levels correlated with growth regulation in 5 of 6 breast and ovarian carcinoma cell lines tested with a trend toward correlation in the sixth. Decreases in DAG may be one mediator of the growth regulatory signals produced by anti-p185c-erbB-2 antibodies.
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PMID:Suppression of diacylglycerol levels by antibodies reactive with the c-erbB-2 (HER-2/neu) gene product p185c-erbB-2 in breast and ovarian cancer cell lines. 969 73

Different epitopes on the extracellular domain of the HER-2 receptor can serve as distinct targets for immunotoxins. To determine the optimal epitope target for immunotoxin therapy, 7 anti-HER-2 ricin A chain murine monoclonal immunotoxins, each reactive with different epitopes of HER-2 receptor, were tested for cytotoxic activity. The immunotoxins produced 1.2-4.6 logs of cytotoxicity in limiting dilution clonogenic assays with 2 breast cancer cell lines that overexpressed HER-2. Cytotoxicity did not correlate with immunoglobulin isotype, binding affinity, relative position of epitopes or internalization of the anti-HER-2 immunotoxins. Interestingly, the most and least effective immunotoxins bound to epitopes in very close proximity. Competitive binding assays with unconjugated antibodies have previously indicated that our antibodies recognized epitopes that are arranged in a linear array. To orient this relative epitope map, deletions were prepared in the HER-2/neu gene and these mutant constructs were expressed in NIH3T3 cells. Epitope expression was determined by antibody binding and radioimmunoassay. Epitopes targeted by the PB3, 454C11 and NB3 antibodies are localized N-terminal to the epitopes recognized by ID5, BD5, 741F8 and 520C9 antibodies. The 2 non-conformational epitopes PB3 and NB3 were localized to regions corresponding to amino acides 78-242 of the p185(HER-2) protein.
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PMID:Relative cytotoxic activity of immunotoxins reactive with different epitopes on the extracellular domain of the c-erbB-2 (HER-2/neu) gene product p185. 1040 66

The relatively high incidence of amplification and overexpression of the neu (c-erb B2/HER-2) oncogene in breast cancer, and its association with poor prognosis, particularly in node negative patients, may allow identification of patients who require aggressive therapy to prevent an early relapse. It's association with ovarian cancer, however, is less well defined than in breast cancer. An ELISA for the c-neu proto-oncogene related protein, p185, has been developed recently using the monoclonal antibodies NB3 and TA1. In the first study of it's kind, we assayed serum samples from patients with primary epithelial ovarian cancer for circulating c-neu p185. Elevated levels were found in 21/178 (11.8%) patients. No correlation was found between serum levels and either the presence or volume of tumor, when assessed either after primary or at second-look surgery. A change in c-neu p185 levels did not correlate with response to chemotherapy. When subjected to univariate and multivariate analyses together with other known prognostic factors, serum c-neu p185 was not a significant predictor of progression-free survival or overall survival. Although c-neu p185 may be involved in the pathogenesis of ovarian cancer, it's assay in serum has no value in prognosis or monitoring.
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PMID:Investigation of the c-neu proto-oncogene related protein, p185, in the serum of primary epithelial ovarian cancer patients. 1157 48