PMID- 15477868 OWN - NLM STAT- MEDLINE DCOM- 20041207 LR - 20220309 IS - 0007-0920 (Print) IS - 1532-1827 (Electronic) IS - 0007-0920 (Linking) VI - 91 IP - 9 DP - 2004 Nov 1 TI - Inverse relationship between ER-beta and SRC-1 predicts outcome in endocrine-resistant breast cancer. PG - 1687-93 AB - 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. FAU - Myers, E AU - Myers E AD - Department of Surgery, Saint Vincent's University Hospital, Dublin 4, Ireland. FAU - Fleming, F J AU - Fleming FJ FAU - Crotty, T B AU - Crotty TB FAU - Kelly, G AU - Kelly G FAU - McDermott, E W AU - McDermott EW FAU - O'higgins, N J AU - O'higgins NJ FAU - Hill, A D K AU - Hill AD FAU - Young, L S AU - Young LS LA - eng PT - Journal Article PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (Antineoplastic Agents, Hormonal) RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogen Receptor beta) RN - 0 (Transcription Factors) RN - 094ZI81Y45 (Tamoxifen) RN - 4TI98Z838E (Estradiol) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Antineoplastic Agents, Hormonal/pharmacology MH - Blotting, Western MH - Breast Neoplasms/drug therapy/*metabolism/pathology MH - Cohort Studies MH - Disease-Free Survival MH - Estradiol/pharmacology MH - Estrogen Receptor alpha/*metabolism MH - Estrogen Receptor beta/*metabolism MH - Female MH - Fluorescent Antibody Technique MH - Histone Acetyltransferases MH - Humans MH - Immunoenzyme Techniques MH - Middle Aged MH - Neoplasms, Hormone-Dependent/drug therapy/*metabolism/pathology MH - Nuclear Receptor Coactivator 1 MH - Receptor, ErbB-2/metabolism MH - Survival Rate MH - Tamoxifen/pharmacology MH - Transcription Factors/*metabolism MH - Treatment Outcome PMC - PMC2409954 EDAT- 2004/10/13 09:00 MHDA- 2004/12/16 09:00 PMCR- 2005/10/12 CRDT- 2004/10/13 09:00 PHST- 2004/10/13 09:00 [pubmed] PHST- 2004/12/16 09:00 [medline] PHST- 2004/10/13 09:00 [entrez] PHST- 2005/10/12 00:00 [pmc-release] AID - 6602156 [pii] AID - 10.1038/sj.bjc.6602156 [doi] PST - ppublish SO - Br J Cancer. 2004 Nov 1;91(9):1687-93. doi: 10.1038/sj.bjc.6602156.