Inverse relationship between ER-beta and SRC-1 predicts outcome in endocrine-resistant breast cancer

Br J Cancer. 2004 Nov 1;91(9):1687-93. doi: 10.1038/sj.bjc.6602156.

Abstract

The oestrogen receptor (ER) interacts with coactivator proteins to modulate genes central to breast tumour progression. Oestrogen receptor is encoded for by two genes, ER-alpha and ER-beta. Although ER-alpha has been well characterized, the role of ER-beta as a prognostic indicator remains unresolved. To determine isoform-specific expression of ER and coexpression with activator proteins, we examined the expression and localisation of ER-alpha, ER-beta and the coactivator protein steroid receptor coactivator 1 (SRC-1) by immunohistochemistry and immunofluorescence in a cohort of human breast cancer patients (n=150). Relative levels of SRC-1 in primary breast cultures derived from patient tumours in the presence of beta-oestradiol and tamoxifen was assessed using Western blotting (n=14). Oestrogen receptor-beta protein expression was associated with disease-free survival (DFS) and inversely associated with the expression of HER2 (P=0.0008 and P<0.0001, respectively), whereas SRC-1 was negatively associated with DFS and positively correlated with HER2 (P<0.0001 and P<0.0001, respectively). Steroid receptor coactivator 1 protein expression was regulated in response to beta-oestradiol or tamoxifen in 57% of the primary tumour cell cultures. Protein expression of ER-beta and SRC-1 was inversely associated (P=0.0001). The association of ER-beta protein expression with increased DFS and its inverse relationship with SRC-1 suggests a role for these proteins in predicting outcome in breast cancer.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / pharmacology
  • Blotting, Western
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cohort Studies
  • Disease-Free Survival
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / metabolism*
  • Estrogen Receptor beta / metabolism*
  • Female
  • Fluorescent Antibody Technique
  • Histone Acetyltransferases
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / metabolism*
  • Neoplasms, Hormone-Dependent / pathology
  • Nuclear Receptor Coactivator 1
  • Receptor, ErbB-2 / metabolism
  • Survival Rate
  • Tamoxifen / pharmacology
  • Transcription Factors / metabolism*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Transcription Factors
  • Tamoxifen
  • Estradiol
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1
  • Receptor, ErbB-2