Short androgen receptor poly-glutamine-promoted endometrial cancer is associated with benzo[a]pyrene-mediated aryl hydrocarbon receptor activation
| Autor: | Chung Lin Wang, Jason Yen Ping Ho, Wen Lung Ma, Bi Hua Cheng, Bo-Ying Bao, Wei-Chung Cheng, Yao Ching Hung, Wei Chun Chang, Lu-Min Chen, Hui-Wen Chang, Qifeng Tang |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
0301 basic medicine medicine.medical_specialty BaP medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Benzo(a)pyrene medicine Humans Gene Tumor Stem Cell Assay Aged Cell Proliferation Gynecology biology Toxin Endometrial cancer AhR Original Articles Cell Biology Middle Aged Aryl hydrocarbon receptor medicine.disease Endometrial Neoplasms poly‐Q polymorphism Androgen receptor Glutamine 030104 developmental biology Receptors Aryl Hydrocarbon chemistry Receptors Androgen 030220 oncology & carcinogenesis endometrial cancer Disease Progression biology.protein Cancer research Molecular Medicine Pyrene Female Original Article Peptides AR |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-1838 |
| DOI: | 10.1111/jcmm.13291 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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