BAG-1 predicts patient outcome and tamoxifen responsiveness in ER-positive invasive ductal carcinoma of the breast

Br J Cancer. 2009 Jan 13;100(1):123-33. doi: 10.1038/sj.bjc.6604809. Epub 2008 Dec 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / chemistry
  • Carcinoma, Ductal, Breast / drug therapy*
  • Carcinoma, Ductal, Breast / pathology
  • Cell Line, Tumor
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Estrogen Antagonists / therapeutic use*
  • Female
  • Humans
  • Immunohistochemistry
  • Neoplasm Invasiveness
  • RNA, Messenger / analysis
  • Receptors, Estrogen / analysis*
  • Tamoxifen / therapeutic use*
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • BCL2-associated athanogene 1 protein
  • DNA-Binding Proteins
  • Estrogen Antagonists
  • RNA, Messenger
  • Receptors, Estrogen
  • Transcription Factors
  • Tamoxifen