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J Cell Mol Med. 2018 Jan;22(1):46-56. doi: 10.1111/jcmm.13291. Epub 2017 Aug 7.

Short androgen receptor poly-glutamine-promoted endometrial cancer is associated with benzo[a]pyrene-mediated aryl hydrocarbon receptor activation.

Author information

1
Graduate Institution of Clinical Medical Science, Graduate Institute of BioMedical Sciences, Department of Pharmacy, China Medical University, Taichung, Taiwan.
2
Sex Hormone Research Center, Department of Obstetrics and Gynecology, Department of Pathology, Research Center for Tumor Medical Science, China Medical University/Hospital, Taichung, Taiwan.
3
Department of OBs & GYN, BenQ Medical Center, Nanjing Medical University, Suzhou, Jiangsu Province, China.
4
Department of Nursing, Asia University, Taichung, Taiwan.
5
Department of OBs& GYN, Chia-Yi Chang-Gong Memorial Hospital, Chia-Yi, Taiwan.
6
Chung-Jen Jounior College of Nursing, Health Sciences and Management, ChiaYi, Taiwan.

Abstract

The androgen receptor (AR) poly-glutamine polymorphism (AR-Q) was reported to play role in endometrial cancer (EMCA) development, yet controversial. Environmental factors interact with genetic variation have been reported in EMCA. Aerosol toxins, polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP), are EMCA facilitators. This report examined the interplay between AR-Qs and BaP in EMCA. During analysing patient AR-Q polymorphism and Aryl hydrocarbon Receptor (AhR) expressions, we found overall survival (OS) benefit is ascending with AR-Q lengths (5-year OS of 61.3% in Q length <20 and 88% in Q length >23). And AhR is higher expressed in short AR-Q tumour compared to that in long AR-Q patient. In vitro study found androgen-response element (ARE) activity descends with AR-Qs length (Q13 > Q25 > Q35), whereas BaP suppresses ARE activities in EMCA cells. Furthermore, AR-Q13 (but not AR-Q25, or -35) enhances BaP-induced dioxin-responsive element (DRE) activity. Lastly, AR-Q13 exerts higher colony-forming capacity than other AR-Qs, and knock-down AhR abolished AR-Q13-mediated colony numbers. This study demonstrated a possible interaction of gene (AR-Q polymorphism) and environmental toxins (e.g. BaP) to affect cancer progression. A large-scale epidemiology and public health survey on the interaction of environmental toxin and AR poly-Q in EMCA is suggested.

KEYWORDS:

AR ; AhR; BaP; endometrial cancer; poly-Q polymorphism

PMID:
28782227
PMCID:
PMC5742722
DOI:
10.1111/jcmm.13291
[Indexed for MEDLINE]
Free PMC Article

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