Journal Article


Leonie S Young
Yvonne Buggy
Niall J O'Higgins
Enda W McDermott
Gabrielle Kelly
Arnold D K Hill
Eddie Myers



immunoprecipitation genetics pathology carcinoma ductal breast proto oncogene protein c ets 2 receptors estrogen nuclear receptor co repressor 1 transcription genetic ets1 protein human fibroblast growth factor 2 ncoa1 protein human transcription factors trans activators nuclear receptor coactivator 3 neoplasm invasiveness immunoenzyme techniques proto oncogene proteins c ets pharmacology survival rate gene expression regulation neoplastic blotting western nuclear receptor coactivator 1 neoplasm recurrence local histone acetyltransferases breast neoplasms repressor proteins receptor erbb 2 prognosis response elements tumor cells cultured ets2 protein human electrophoretic mobility shift assay proto oncogene protein c ets 1 ncor1 protein human epidermal growth factor metabolism humans nuclear proteins proto oncogene proteins female

Associations and interactions between Ets-1 and Ets-2 and coregulatory proteins, SRC-1, AIB1, and NCoR in breast cancer. (2005)

Abstract Associations between p160 coactivator proteins and the development of resistance to endocrine treatment have been described. We hypothesized that nuclear receptor coregulatory proteins may interact with nonsteroid receptors. We investigated the mitogen-activated protein kinase-activated transcription factors, Ets, as possible interaction proteins for the coactivators SRC-1 and AIB1 and the corepressor NCoR in human breast cancer. Expression and coexpression of Ets and the coregulatory proteins was investigated using immunohistochemistry and immunofluorescence in a cohort of breast tumor patients (N = 134). Protein expression, protein-DNA interactions and protein-protein interactions were assessed using Western blot, electromobility shift, and coimmunoprecipitation analysis, respectively. Ets-1 and Ets-2 associated with reduced disease-free survival (P < 0.0292, P < 0.0001, respectively), whereas NCoR was a positive prognostic indicator (P < 0.0297). Up-regulation of Ets-1 protein expression in cell cultures derived from patient tumors in the presence of growth factors associated with tumor grade (P < 0.0013; n = 28). In primary breast tumor cell cultures and in the SKBR3 breast cell line, growth factors induced interaction between Ets and their DNA response element, induced recruitment of coactivators to the transcription factor-DNA complex, and up-regulated protein expression of HER2. Ets-1 and Ets-2 interacted with the coregulators under basal conditions, and growth factors up-regulated Ets-2 interaction with SRC-1 and AIB1. Coexpression of Ets-2 and SRC-1 significantly associated with the rate of recurrence and HER expression, compared with patients who expressed Ets-2 but not SRC-1 (P < 0.0001 and P < 0.0001, respectively). These data describe associations and interactions between nonsteroid transcription factors and coregulatory proteins in human breast cancer.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Leonie S Young, Yvonne Buggy, Niall J O'Higgins, Enda W McDermott, Gabrielle Kelly, Arnold D K Hill, Eddie Myers

Experts in our system

Leonie S Young
Royal College of Surgeons in Ireland
Total Publications: 42
E W McDermott
University College Dublin
Total Publications: 49
Gabrielle Kelly
University College Dublin
Total Publications: 9
Arnold D K Hill
Royal College of Surgeons in Ireland
Total Publications: 110