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

Studies with human breast cancer cell lines have shown a causal association between overexpression of the HER-2/neu proto-oncogene receptor and the acquisition of resistance to tamoxifen. Some clinical studies also indicate that patients with tumors showing high HER-2 levels or high levels of the circulating ectodomain of HER-2 may have a lower response to tamoxifen compared with tumors with low HER-2 levels or low circulating ectodomain. Treatment with anti-HER-2 antibodies seems to restore tamoxifen activity in some experimental systems. However, whether anti-HER-2 therapies will increase tamoxifen action and/or reverse this putative oncogene-mediated resistance in patients with estrogen receptor-positive, hormone-dependent tumors, is unclear. We are conducting a phase II trial of a humanized anti-HER-2 monoclonal antibody, trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) in combination with tamoxifen in patients with estrogen receptor-positive metastatic breast cancer. Other prospective randomized clinical trials are needed to directly evaluate the contribution of HER-2 signaling to antiestrogen resistance in vivo.
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PMID:Ongoing and planned trials of hormonal therapy and trastuzumab. 1123 26

Gene amplification is an important mechanism of oncogene activation in breast and other cancers. Characterization of amplified regions of the genome in breast cancer has led to the identification of important oncogenes including erbB-2/HER-2, C-MYC, and fibroblast growth factor receptor (FGFR) 2. Chromosome 8p11-p12 is amplified in 10-15% of human breast cancers. The putative oncogene FGFR1 localizes to this region; however, we show evidence that FGFR inhibition fails to slow growth of three breast cancer cell lines with 8p11-p12 amplification. We present a detailed analysis of this amplicon in three human breast cancer cell lines using comparative genomic hybridization, traditional Southern and Northern analysis, and chromosome 8 cDNA microarray expression profiling. This study has identified new candidate oncogenes within the 8p11-p12 region, supporting the hypothesis that genes other than FGFR1 may contribute to oncogenesis in breast cancers with proximal 8p amplification.
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PMID:Genomic and expression analysis of the 8p11-12 amplicon in human breast cancer cell lines. 1472 6