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

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.

Increase Paclitaxel Sensitivity to Better Suppress Serous Epithelial Ovarian Cancer via Ablating Androgen Receptor/Aryl Hydrocarbon Receptor-ABCG2 Axis

“…et al [32]; however, whether an environmental stimulant is involved in AR transactivation remains unknown. Our own previous work showed that the interaction of AR/AhR promoted endometrial cancer progression under AhR ligand (TCDD) treatment [31]. In the present report, we found that there is an alternative ARE, located on the ABCG2 promoter, which could be activated by the xenobiotic receptor AhR, and form an AR/AhR complex.…”

“…NC_018915) (Figure S2). According to previous studies [29,30] and our recent study in AhR [31], we hypothesized that the AR–AhR complex could also be observed in EOC cells. As demonstrated in Figure 1D, using a co-immunoprecipitation (co-IP) assay we were able to observe AR–AhR interactions in the three serous EOC cell lines.…”

“…The histological studies were performed with modifications as described in previous studies [31,54]. For histologic inspection, we treated tissue sections (2 μM) with hematoxylin and eosin, or stained sections with antibody specific to AR and ABCG2 while using an ABC kit (Vector Laboratories, CA, USA) to enhance the staining signals.…”

LDLR-mediated lipidome–transcriptome reprogramming in cisplatin insensitivity

“…In general, the histological studies were performed as described in previous studies (Hung et al 2014, Chen et al 2018 with some modifications. For general histologic inspection, we treated the tissue sections (2 μM) with H&E or stained the sections with antibodies specific for LDLR and lipoprotein lipase (LPL) with an ABC kit (Vector Laboratories) to enhance the staining signals.…”

Low-Density Lipoprotein Receptor-Mediated Lipidome-Transcriptome Reprogramming Impulses to Cisplatin Insensitivity

“…Immunohistochemistry and quantitation of staining score: In general, the histological studies were performed as described in previous studies (Chen, Bao et al, 2018 with some modifications. For general histologic inspection, we treated the tissue sections (2 μM) with hematoxylin and eosin or stained the sections with antibodies specific for LDLR and LPL with an ABC kit (Vector Laboratories) to enhance the staining signals.…”