title: The AhR Ligand, TCDD, Regulates Androgen Receptor Activity Differently in Androgen-Sensitive versus Castration-Resistant Human Prostate Cancer Cells.
abstract: The reported biological effects of TCDD include induction of drug metabolizing enzymes, wasting syndrome and tumor promotion. TCDD elicits most of its effects through binding the aryl hydrocarbon receptor (AhR). TCDD induced degradation of AhR has been widely reported and requires ubiquitination of the protein. The rapid depletion of AhR following TCDD activation serves as a mechanism to modulate AhR mediated gene induction. In addition to inducing AhR degradation, TCDD has been reported to induce degradation of hormone receptors. The studies reported here, evaluate the effect of TCDD exposure on androgen receptor (AR) expression and activity in androgen-sensitive LNCaP and castration-resistant C4-2 prostate cancer cells. Our results show that TCDD exposure does not induce AhR or AR degradation in C4-2 cells. However, both AhR and AR are degraded in LNCaP cells following TCDD exposure. In addition, TCDD enhances AR phosphorylation and induces expression of AR responsive genes in LNCaP cells. Our data reveals that TCDD effect on AR expression and activity differs in androgen-sensitive and castration-resistant prostate cancer cell models.
authors.affiliation: Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley Drive, S.W. Atlanta, GA 30314, USA. maryam.ghotbaddini@students.cau.edu.|Center for Cancer Research and Therapeutic Development (CCRTD), Clark Atlanta University, 223 James P. Brawley Drive, S.W., Atlanta, GA 30314, USA. maryam.ghotbaddini@students.cau.edu.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ghotbaddini
authors.affiliation: Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley Drive, S.W. Atlanta, GA 30314, USA. jpowell@cau.edu.|Center for Cancer Research and Therapeutic Development (CCRTD), Clark Atlanta University, 223 James P. Brawley Drive, S.W., Atlanta, GA 30314, USA. jpowell@cau.edu.
authors.forename: Joann B
authors.initials: JB
authors.lastname: Powell
mesh_terms: D002369:Castration; D045744:Cell Line, Tumor / Q000187:drug effects*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D006801:Humans; D008024:Ligands; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011471:Prostatic Neoplasms; D011944:Receptors, Androgen / Q000187:drug effects*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C410798:AR protein, human; D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1
keywords: AhR; TCDD/dioxin; androgen receptor; castration-resistant; prostate cancer