Type

Journal Article

Authors

Leonie S Young
Arnold D K Hill
Stephen Pennington
Peadar O'Gaora
Sarah Early
Damian McCartan
Marie McIlroy

Subjects

Biochemistry

Topics
breast neoplasms s100 proteins tumor cells cultured disease free survival gene regulatory networks humans metabolism ncoa1 protein human female protein binding therapeutic use s 100 calcium binding protein beta subunit genetics diagnosis drug therapy blood case control studies genes developmental physiology homeodomain proteins transcription factors hoxc11 protein human antineoplastic agents hormonal prognosis gene expression regulation neoplastic drug resistance neoplasm nerve growth factors nuclear receptor coactivator 1

Interaction of developmental transcription factor HOXC11 with steroid receptor coactivator SRC-1 mediates resistance to endocrine therapy in breast cancer [corrected]. (2010)

Abstract Mechanisms of acquired resistance to endocrine therapy in breast cancer, a major clinical challenge, are poorly understood. We have used a mass spectrometry-based screen to identify proteins that are associated with the endocrine-resistant phenotype. In this study, we report the identification of a novel pathway of resistance to endocrine therapy involving interactions of the developmental transcription HOXC11 with the steroid receptor coactivator protein SRC-1, which is a strong predictor of reduced disease-free survival in breast cancer patients. HOXC11 and SRC-1 cooperate to regulate expression of the calcium-binding protein S100beta in resistant breast cancer cells. Nuclear HOXC11 and S100beta were found to strongly predict poor disease-free survival in breast cancer patients (n = 560; hazard ratios: 5.79 and 5.82, respectively; P < 0.0001). Elevated serum levels of S100beta detected in patients also predicted reduced disease-free survival (n = 80; hazard ratio: 5.3; P = 0.004). Our findings define a biomolecular interaction network that drives an adaptive response to endocrine therapy with negative consequences for survival in breast cancer.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Leonie S Young, Arnold D K Hill, Stephen Pennington, Peadar O'Gaora, Sarah Early, Damian McCartan, Marie McIlroy

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
 
3
Stephen R Pennington
University College Dublin
 
4
Peadar O'Gaora
University College Dublin
Total Publications: 11
 
5
Marie McIlroy
Royal College of Surgeons in Ireland