Type

Journal Article

Authors

Leonie S Young
Arnold D K Hill
Yvonne Buggy
Fergal J Fleming
Marie Mc Ilroy

Subjects

Biochemistry

Topics
breast neoplasms receptor erbb 2 electrophoretic mobility shift assay tumor cells cultured cell proliferation promoter regions genetic ncoa3 protein human trans activators therapeutic use humans metabolism estrogen receptor beta response elements tamoxifen female immunoprecipitation antagonists inhibitors genetics pathology presenilin 2 estrogen receptor alpha neoplasms hormone dependent drug therapy nuclear receptor coactivator 3 antineoplastic agents hormonal middle aged psen2 protein human fluorescent antibody technique drug resistance neoplasm neoplasm recurrence local histone acetyltransferases blotting western

Tamoxifen-induced ER-alpha-SRC-3 interaction in HER2 positive human breast cancer; a possible mechanism for ER isoform specific recurrence. (2006)

Abstract Differential signalling between the two oestrogen receptor (ER) isoforms in the presence of tamoxifen has been described. We hypothesise that differential recruitment of the steroid receptor co-activator, SRC-3 to ER-alpha and ER-beta may in part explain associations between ER isoforms and response to endocrine treatment. SRC-3 was localised within epithelial cells of breast tumour tissue and was co-localised with ER-alpha and ER-beta, (n=112). Expression of SRC-3 was found to be positively associated with ER-alpha (P=0.0021) and inversely with ER-beta (P<0.0001). Uniquely, this study utilises primary cell cultures derived from patient tumours, thus providing samples not readily available in most molecular model systems. These samples have enabled us to investigate the influence of growth factor pathways on steroid receptor-co-activator interactions. In HER2 (human epidermal growth factor receptor 2) positive primary tumour cell cultures 17beta-estradiol induced a decrease in SRC-3, whereas upregulated SRC-3 expression. Furthermore, treatment with tamoxifen-induced SRC-3 recruitment to the ER-oestrogen response element and enhanced interaction between SRC-3 and ER-alpha, but not ER-beta. Knockdown of SRC-3 results in a concomitant loss of expression of the oestrogen target gene pS2. Furthermore, silencing of SRC-3 resensitizes endocrine resistant, HER2 positive cells to the anti-proliferative effects of tamoxifen. The ability of ER-alpha, but not ER-beta to recruit SRC-3 in the presence of tamoxifen may in part explain the differential ER isoform associations with recurrence in human breast cancer.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Leonie S Young, Arnold D K Hill, Yvonne Buggy, Fergal J Fleming, Marie Mc Ilroy

Experts in our system

1
Leonie S Young
Royal College of Surgeons in Ireland
Total Publications: 42
 
2
Arnold D K Hill
Royal College of Surgeons in Ireland
Total Publications: 110