Type

Journal Article

Authors

Leonie S Young
Arnold D Hill
Thomas B Crotty
Mary F Dillon
Marie McIlroy
Anthony T Stafford
Fiona T Bane
Aisling M Redmond

Subjects

Biochemistry

Topics
breast neoplasms prognosis etiology ncoa3 protein human tissue array analysis ncoa1 protein human disease free survival humans nucleocytoplasmic transport proteins tamoxifen nuclear proteins female therapeutic use cell line tumor chemistry drug therapy estrogen receptor alpha human estrogen receptor alpha trans activators nuclear receptor coactivator 3 mortality physiology mybbp1a protein human transcription factors drug resistance neoplasm nuclear receptor coactivator 1 neoplasm recurrence local histone acetyltransferases

Coassociation of estrogen receptor and p160 proteins predicts resistance to endocrine treatment; SRC-1 is an independent predictor of breast cancer recurrence. (2009)

Abstract This study investigates the role of the p160 coactivators AIB1 and SRC-1 independently, and their interactions with the estrogen receptor, in the development of resistance to endocrine treatments. The expression of the p160s and the estrogen receptor, and their interactions, was analyzed by immunohistochemistry and quantitative coassociation immunofluorescent microscopy, using cell lines, primary breast tumor cell cultures, and a tissue microarray with breast cancer samples from 560 patients. Coassociation of the p160s and estrogen receptor alpha was increased in the LY2 endocrine-resistant cell line following treatment with tamoxifen in comparison with endocrine-sensitive MCF-7 cells. In primary cultures, there was an increase in association of the coactivators with estrogen receptor alpha following estrogen treatment but dissociation was evident with tamoxifen. Immunohistochemical staining of the tissue microarray revealed that SRC-1 was a strong predictor of reduced disease-free survival (DFS), both in patients receiving adjuvant tamoxifen treatment and untreated patients (P < 0.0001 and P = 0.0111, respectively). SRC-1 was assigned a hazard ratio of 2.12 using a Cox proportional hazards model. Endocrine-treated patients who coexpressed AIB1 with human epidermal growth factor receptor 2 had a significantly shorter DFS compared with all other patients (P = 0.03). Quantitative coassociation analysis in the patient tissue microarray revealed significantly stronger colocalization of AIB1 and SRC-1 with estrogen receptor alpha in patients who have relapsed in comparison with those patients who did not recur (P = 0.026 and P = 0.00001, respectively). SRC-1 is a strong independent predictor of reduced DFS, whereas the interactions of the p160 proteins with estrogen receptor alpha can predict the response of patients to endocrine treatment.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Leonie S Young, Arnold D Hill, Thomas B Crotty, Mary F Dillon, Marie McIlroy, Anthony T Stafford, Fiona T Bane, Aisling M Redmond

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
Marie McIlroy
Royal College of Surgeons in Ireland
 
4
Fiona T Bane
Royal College of Surgeons in Ireland
Total Publications: 9
 
5
Aisling M Redmond
Royal College of Surgeons in Ireland
Total Publications: 7