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

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

E Myers  1 , F J Fleming, T B Crotty, G Kelly, E W McDermott, N J O'higgins, A D K Hill, L S Young
Affiliations

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

E Myers et al. Br J 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-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.

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Figures

Figure 1
Figure 1
ER-α, ER-β and SRC-1 protein expression in paraffin-embedded invasive breast carcinoma and normal breast tissue specimens. (A) Immunohistochemical localisation of ER-α, ER-β and SRC-1 (× 200) in primary breast cancer counterstained with haematoxylin and matched IgG controls. (B) ER-α, ER-β and SRC-1, (× 200) protein expression in normal breast tissue. (C) Immunofluorescent colocalisation of ER-α with SRC-1 (× 200) and ER-β with SRC-1 (× 200) invasive breast carcinoma.
Figure 2
Figure 2
Kaplan–Meier estimates of disease-free survival (DFS). (A) Disease-free survival according to ER-β expression and (B) according to SRC-1 expression.
Figure 3
Figure 3
Western blot analysis of SRC-1 protein levels in primary breast cultures. (A) Illustrative blots of primary breast tumour response to steroid environment; patient A – increased expression of SRC-1 in response to oestrogen, patient B – nonresponder to oestrogen or tamoxifen, patient C – decreased expression of SRC-1 in response to tamoxifen. (B) Relative optical density of SRC-1 immunoblots. Optical density readings of control values were normalised to 1 and treated groups were expressed as a ratio. Values are expressed as mean±s.e.m. (n=14).
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