Type

Journal Article

Authors

Leonie S Young
Peadar O'Gaora
Arnold D Hill
Jianming Xu
Marie McIlroy
Li Qin
Yuan Hao
Christopher Byrne
Ailis Fagan
Jarlath C Bolger
and 1 others

Subjects

Biochemistry

Topics
humans pharmacology metabolism physiology antineoplastic agents hormonal female animals drug resistance neoplasm genetics mice pathology nerve tissue proteins nuclear receptor coactivator 1 transcriptome adam22 protein human cell line tumor breast neoplasms adam proteins mice inbred balb c receptors estrogen

Global characterization of the SRC-1 transcriptome identifies ADAM22 as an ER-independent mediator of endocrine-resistant breast cancer. (2011)

Abstract The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity that permits the emergence of a hormone-independent tumor. The steroid coactivator protein SRC-1, through interactions with developmental proteins and other nonsteroidal transcription factors, drives this tumor adaptability. In this discovery study, we identified ADAM22, a non-protease member of the ADAM family of disintegrins, as a direct estrogen receptor (ER)-independent target of SRC-1. We confirmed SRC-1 as a regulator of ADAM22 by molecular, cellular, and in vivo studies. ADAM22 functioned in cellular migration and differentiation, and its levels were increased in endocrine resistant-tumors compared with endocrine-sensitive tumors in mouse xenograft models of human breast cancer. Clinically, ADAM22 was found to serve as an independent predictor of poor disease-free survival. Taken together, our findings suggest that SRC-1 switches steroid-responsive tumors to a steroid-resistant state in which the SRC-1 target gene ADAM22 has a critical role, suggesting this molecule as a prognostic and therapeutic drug target that could help improve the treatment of endocrine-resistant breast cancer.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Leonie S Young, Peadar O'Gaora, Arnold D Hill, Jianming Xu, Marie McIlroy, Li Qin, Yuan Hao, Christopher Byrne, Ailis Fagan, Jarlath C Bolger and 1 others

Experts in our system

1
Leonie S Young
Royal College of Surgeons in Ireland
Total Publications: 42
 
2
Peadar O'Gaora
University College Dublin
Total Publications: 11
 
3
Arnold D K Hill
Royal College of Surgeons in Ireland
Total Publications: 110
 
4
Marie McIlroy
Royal College of Surgeons in Ireland
 
5
Yuan Hao
Royal College of Surgeons in Ireland
Total Publications: 5
 
6
Christopher Byrne
Royal College of Surgeons in Ireland
Total Publications: 13
 
7
AilĂ­s Fagan
Royal College of Surgeons in Ireland
Total Publications: 13