Type

Journal Article

Authors

Leonie S Young
Arnold D K Hill
Paul Tibbitts
Jane O'Hara
Stephen Sande
Sinéad Cocchiglia
Éamon Hughes
Christopher Byrne
Sarah M Theissen
Jean McBryan

Subjects

Medicine & Nursing

Topics
female metabolism disease progression drug therapy transfection neoplasm metastasis tamoxifen nuclear receptor coactivator 1 humans cell line tumor breast neoplasms pharmacology aromatase inhibitors

Metastatic progression with resistance to aromatase inhibitors is driven by the steroid receptor coactivator SRC-1. (2011)

Abstract Aromatase inhibitors (AI) are a standard-of-care treatment for postmenopausal, estrogen receptor-positive breast cancers. Although tumor recurrence on AI therapy occurs, the mechanisms underlying acquired resistance to AIs remain unknown. In this study, we examined a cohort of endocrine-treated breast cancer patients and used a cell line model of resistance to the AI letrozole. In patients treated with a first-line AI, hormone receptor switching between primary and resistant tumors was a common feature of disease recurrence. Resistant cells exhibited a switch from steroid-responsive growth to growth factor-responsive and endocrine-independent growth, which was accompanied by the development of a more migratory and disorganized phenotype. Both the resistant cells and tumors from AI-resistant patients showed high expression of the steroid receptor coactivator SRC-1. Direct interactions between SRC-1 and the transcription factor Ets2 regulated Myc and MMP9. SRC-1 was required for the aggressive and motile phenotype of AI-resistant cells. Interestingly, SRC-1 expression in primary and/or recurrent tumors was associated with a reduction in disease-free survival in treated patients. Moreover, there was a significant association between SRC-1 and Ets2 in the recurrent tissue compared with the matched primary tumor. Together, our findings elucidate a mechanism of AI-specific metastatic progression in which interactions between SRC-1 and Ets2 promote dedifferentiation and migration in hormone-dependent 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, Paul Tibbitts, Jane O'Hara, Stephen Sande, Sinéad Cocchiglia, Éamon Hughes, Christopher Byrne, Sarah M Theissen, Jean McBryan

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
Paul Tibbitts
Royal College of Surgeons in Ireland
Total Publications: 11
 
4
Sinéad Cocchiglia
Royal College of Surgeons in Ireland
Total Publications: 10
 
5
Éamon Hughes
Royal College of Surgeons in Ireland
Total Publications: 3
 
6
Christopher Byrne
Royal College of Surgeons in Ireland
Total Publications: 13
 
7
Jean McBryan
Royal College of Surgeons in Ireland
Total Publications: 10