Inhibition of androgen receptor and Cdc25A phosphatase as a combination targeted therapy in molecular apocrine breast cancer

2010 ◽  
Vol 298 (1) ◽  
pp. 74-87 ◽  
Author(s):  
Ali Naderi ◽  
Ji Liu
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Molecular Apocrine ◽  
Cdc25a Phosphatase

scholarly journals Androgen Receptor, EGFR, and BRCA1 as Biomarkers in Triple-Negative Breast Cancer: A Meta-Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Li Zhang ◽  
Cheng Fang ◽  
Xianqun Xu ◽  
Anling Li ◽  
Qing Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Meta Analysis ◽  
Brca1 Mutation ◽  
Expression Level ◽  
Breast Cancer Susceptibility Gene ◽  
Egfr Expression

Objective. More and more evidences demonstrate that androgen receptor (AR), epidermal growth factor receptor (EGFR), and breast cancer susceptibility gene 1 (BRCA1) have unique clinical implications for targeted therapy or prognosis in triple-negative breast cancer (TNBC). Therefore, we conducted a meta-analysis to summarize the possible associations.Methods. We retrieved published articles about AR, EGFR, and BRCA1 in TNBC from PubMed and EMBASE. The analysis was performed with Rev-Man 5.2 software.Results. A total of 38 articles were eligible for the meta-analysis. Our study showed that the expression level of EGFR (OR=6.88,P<0.00001) and the prevalence of BRCA1 mutation (RR=5.26,P<0.00001) were higher in TNBC than non-TNBC. In contrast, the expression level of AR was lower in TNBC than non-TNBC (OR=0.07,P<0.00001). In the subgroup related to EGFR expression, the level of EGFR expression was significantly increased in Asians (OR=9.60) compared with Caucasians (OR=5.53) for TNBC patients. Additionally, the prevalence of BRCA1 mutation in Asians (RR=5.43,P<0.00001) was higher than that in Caucasians (RR=5.16,P<0.00001).Conclusions. The distinct expression of AR and EGFR and the prevalence of BRCA1 mutation indicated that AR, EGFR, and BRCA1 might be unique biomarkers for targeted therapy and prognosis in TNBC.

scholarly journals Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1

2011 ◽  
Vol 30 (15) ◽  
pp. 3019-3027 ◽  
Author(s):  
Jessica L L Robinson ◽  
Stewart MacArthur ◽  
Caryn S Ross-Innes ◽  
Wayne D Tilley ◽  
David E Neal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Molecular Apocrine

Androgen receptor- and PIAS1-regulated gene programs in molecular apocrine breast cancer cells

2015 ◽  
Vol 414 ◽  
pp. 91-98 ◽  
Author(s):  
Marjo Malinen ◽  
Sari Toropainen ◽  
Tiina Jääskeläinen ◽  
Biswajyoti Sahu ◽  
Olli A. Jänne ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Apocrine

The androgen receptor as a surrogate marker for molecular apocrine breast cancer subtyping

The Breast ◽  
2014 ◽  
Vol 23 (3) ◽  
pp. 234-243 ◽  
Author(s):  
Sotiris Lakis ◽  
Vassiliki Kotoula ◽  
Anastasia G. Eleftheraki ◽  
Anna Batistatou ◽  
Mattheos Bobos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Surrogate Marker ◽  
Molecular Apocrine

Enobosarm: A targeted therapy for metastatic, androgen receptor positive, breast cancer.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 568-568 ◽  
Author(s):  
Beth Overmoyer ◽  
Pedro Sanz-Altamira ◽  
Ryan P. Taylor ◽  
Michael L. Hancock ◽  
James T. Dalton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Positive Breast Cancer

scholarly journals Vitamin D and androgen receptor-targeted therapy for triple-negative breast cancer

2016 ◽  
Vol 157 (1) ◽  
pp. 77-90 ◽  
Author(s):  
A. Thakkar ◽  
B. Wang ◽  
M. Picon-Ruiz ◽  
P. Buchwald ◽  
Tan A. Ince
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative

Androgen Receptor-Targeted Therapy for Breast Cancer

2017 ◽  
Vol 9 (4) ◽  
pp. 242-250
Author(s):  
Tomas G. Lyons ◽  
Tiffany A. Traina
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Targeted Therapy

scholarly journals An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity

2012 ◽  
Vol 19 (4) ◽  
pp. 599-613 ◽  
Author(s):  
Nicole L Moore ◽  
Grant Buchanan ◽  
Jonathan M Harris ◽  
Luke A Selth ◽  
Tina Bianco-Miotto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Ligand Binding ◽  
Cell Line ◽  
Breast Cancer Subtype ◽  
Wnt Signaling Pathway ◽  
Intramolecular Interactions ◽  
Gene Set Enrichment Analysis ◽  
Molecular Apocrine ◽  
Cancer Subtype

Recent evidence indicates that the estrogen receptor-α-negative, androgen receptor (AR)-positive molecular apocrine subtype of breast cancer is driven by AR signaling. The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype; its proliferation is stimulated by androgens such as 5α-dihydrotestosterone (DHT) but inhibited by the progestin medroxyprogesterone acetate (MPA) via AR-mediated mechanisms. We report here that theARgene in MDA-MB-453 cells contains a G-T transversion in exon 7, resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 (Q865H) in the ligand binding domain. Compared with wild-type AR, the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists. Ligand binding, molecular modeling, mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation, AR intramolecular interactions, and receptor stability. Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells. Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway. These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant. This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype.

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