期刊
BRITISH JOURNAL OF CANCER
卷 100, 期 1, 页码 123-133出版社
SPRINGERNATURE
DOI: 10.1038/sj.bjc.6604809
关键词
breast cancer; prognosis; response marker; BAG-1; tamoxifen sensitivity
类别
资金
- Cancer Institute NSW
- National Health and Medical Research Council of Australia (NHMRC)
- Petre Foundation
- RT Hall Trust
BAG-1 (bcl-2-associated athanogene) enhances oestrogen receptor ( ER) function and may influence outcome and response to endocrine therapy in breast cancer. We determined relationships between BAG-1 expression, molecular phenotype, response to tamoxifen therapy and outcome in a cohort of breast cancer patients and its influence on tamoxifen sensitivity in MCF-7 breast cancer cells in vitro. Publically available gene expression data sets were analysed to identify relationships between BAG-1 mRNA expression and patient outcome. BAG-1 protein expression was assessed using immunohistochemistry in 292 patients with invasive ductal carcinoma and correlated with clinicopathological variables, therapeutic response and disease outcome. BAG-1-overexpressing MCF-7 cells were treated with antioestrogens to assess its effects on cell proliferation. Gene expression data demonstrated a consistent association between high BAG-1 mRNA and improved survival. In ER+ cancer (n = 189), a high nuclear BAG-1 expression independently predicted improved outcome for local recurrence (P = 0.0464), distant metastases (P = 0.0435), death from breast cancer (P = 0.009, hazards ratio 0.29, 95% CI: 0.114-0.735) and improved outcome in tamoxifen-treated patients (n = 107; P = 0.0191). BAG-1 overexpression in MCF-7 cells augmented antioestrogen-induced growth arrest. A high BAG-1 expression predicts improved patient outcome in ER+ breast carcinoma. This may reflect both a better definition of the hormone-responsive phenotype and a concurrent increased sensitivity to tamoxifen.
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