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

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-α and ER-β. Although ER-α has been well characterized, the role of ER-β 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-α, ER-β 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 β-oestradiol and tamoxifen was assessed using Western blotting (n=14). Oestrogen receptor-β 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 β-oestradiol or tamoxifen in 57% of the primary tumour cell cultures. Protein expression of ER-β and SRC-1 was inversely associated (P=0.0001). The association of ER-β protein expression with increased DFS and its inverse relationship with SRC-1 suggests a role for these proteins in predicting outcome in breast cancer.