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Short androgen receptor poly-glutamine-promoted endometrial cancer is associated with benzo[a]pyrene-mediated aryl hydrocarbon receptor activation
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
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 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15821838
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....1f0349cdcd72606ed60b0386a98b05db