Ghotbaddini Maryam, Powell Joann B
Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley Drive, S.W. Atlanta, GA 30314, USA.
Center for Cancer Research and Therapeutic Development (CCRTD), Clark Atlanta University, 223 James P. Brawley Drive, S.W., Atlanta, GA 30314, USA.
Int J Environ Res Public Health. 2015 Jul 6;12(7):7506-18. doi: 10.3390/ijerph120707506.
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.
据报道，2,3,7,8-四氯二苯并对二恶英（TCDD）的生物学效应包括诱导药物代谢酶、消瘦综合征和肿瘤促进作用。TCDD通过与芳烃受体（AhR）结合引发其大部分效应。TCDD诱导AhR降解已被广泛报道，且该过程需要蛋白质的泛素化。TCDD激活后AhR的快速耗竭是调节AhR介导的基因诱导的一种机制。除了诱导AhR降解外，据报道TCDD还可诱导激素受体降解。此处报道的研究评估了TCDD暴露对雄激素敏感的LNCaP和去势抵抗性C4-2前列腺癌细胞中雄激素受体（AR）表达和活性的影响。我们的结果表明，TCDD暴露不会诱导C4-2细胞中AhR或AR降解。然而，TCDD暴露后，LNCaP细胞中的AhR和AR均会降解。此外，TCDD增强LNCaP细胞中AR的磷酸化并诱导AR反应性基因的表达。我们的数据表明，TCDD对AR表达和活性的影响在雄激素敏感和去势抵抗性前列腺癌细胞模型中有所不同。
