Type

Journal Article

Authors

Michael Duffy
John Crown
Norma O'Donovan
Elizabeth J Ryan
Naoise C Synnott
Stephen F Madden
Alyson Murray
Francesco Caiazza

Subjects

Biochemistry

Topics
gene expression cancer cell lines cancer cells cell migration triple negative breast cancer transcription factors pre clinical cell growth

Pre-clinical evaluation of the AR inhibitor enzalutamide in triple negative breast cancer cells. (2016)

Abstract The androgen receptor (AR) is present in approximately 80% of invasive breast cancer, and in up to 30% of patients with triple-negative breast cancer (TNBC). Our aim was therefore to investigate the targeting of AR as a possible hormonal approach to the treatment of TNBC. IC50 values for the second-generation anti-androgen enzalutamide across 11 breast cancer cell lines varied from 4 µM to > 50 µM. The activity of enzalutamide was similar in TN and non-TN cell lines but was dependent on the presence of AR. Enzalutamide reduced clonogenic potential and cell growth in a 3D matrix in AR-positive cells. In addition, enzalutamide also inhibited cell migration and invasion in an AR-dependent manner. Enzalutamide appeared to mediate these processes through downregulation of the transcription factors AP-1 and SP-1. The first generation anti-androgen flutamide similarly blocked cell growth, migration and invasion. AR-positive TNBC cells clustered separately from AR-negative cells based on an androgen-related gene expression signature, independently on TNBC subtype. Analysis of 2091 patients revealed an association between AR expression and poor overall survival, selectively in patients with the basal sub-type of breast cancer, the vast majority of which are TN. We conclude that targeting of the AR with drugs such as enzalutamide may provide an alternative treatment strategy for patients with AR-positive TNBC.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

Michael Duffy, John Crown, Norma O'Donovan, Elizabeth J Ryan, Naoise C Synnott, Stephen F Madden, Alyson Murray, Francesco Caiazza

Experts in our system

1
Michael J Duffy
University College Dublin
 
2
John Crown
Dublin City University
Total Publications: 104
 
3
Norma O'Donovan
Dublin City University
Total Publications: 59
 
4
Elizabeth J Ryan
University College Dublin
 
5
Naoise C Synnott
Dublin City University
 
6
Stephen F Madden
Dublin City University
Total Publications: 45
 
7
Alyson Murray
Dublin City University
Total Publications: 6
 
8
Francesco Caiazza
Trinity College Dublin
Total Publications: 4