Open AccessShort androgen receptor poly‐glutamine‐promoted endometrial cancer is associated with benzo[a]pyrene‐mediated aryl hydrocarbon receptor activation
Author(s) -
Chen Lumin,
Bao BoYing,
Chang WeiChun,
Ho Jason YenPing,
Cheng BiHua,
Wang ChungLin,
Tang Qifeng,
Cheng WeiChung,
Chang HuiWen,
Hung YaoChing,
Ma WenLung
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13291
Subject(s) - androgen receptor , aryl hydrocarbon receptor , pyrene , benzo(a)pyrene , chemistry , receptor , endometrial cancer , biology , cancer research , gene , genetics , biochemistry , cancer , prostate cancer , transcription factor , organic chemistry
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.