Abstract 1043: Blocking constitutive aryl hydrocarbon receptor (AhR) signaling attenuates androgen receptor activity
| Autor: | Maryam Ghotbaddini, Aaron Hemphill, Joann B. Powell |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Cancer Research. 75:1043-1043 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2015-1043 |
| Popis: | PURPOSE: The aryl hydrocarbon receptor (AhR) is a member of the basic-helix-loop-helix family of transcription factors. AhR is widely known for regulating the transcription of drug metabolizing enzymes involved in the xenobiotic metabolism of carcinogens and therapeutic agents, such as cytochrome P450-1B1 (CYP1B1). Additionally, AhR has also been reported to interact with multiple signaling pathways during prostate development. Here we investigate the effect of sustained AhR signaling on androgen receptor function in prostate cancer cells. METHODS/RESULTS: Immunoblot analysis shows that AhR expression is increased in androgen independent (C4-2) prostate cancer cells when compared to androgen sensitive (LNCaP) cells. qRT-PCR studies revealed constitutive AhR signaling in C4-2 cells without the ligand induced activation required in LNCaP cells. A reduction of AhR activity by short RNA mediated silencing in C4-2 cells reduced expression of both AhR and androgen responsive genes. The decrease in androgen responsive genes correlates to a decrease in phosphorylated androgen receptor and androgen receptor expression in the nucleus. CONCLUSION: These data indicates that AhR is required to maintain hormone independent signaling by the androgen receptor in C4-2 cells. Collectively, these data provide evidence of a direct role for AhR in androgen independent signaling and provides insight into the molecular mechanisms responsible for sustained androgen receptor signaling in hormone refractory prostate cancer. These studies were supported by the RCMI grant 2G12RR003062-22. Citation Format: Maryam Ghotbaddini, Aaron Hemphill, Joann B. Powell. Blocking constitutive aryl hydrocarbon receptor (AhR) signaling attenuates androgen receptor activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1043. doi:10.1158/1538-7445.AM2015-1043 |
| Databáze: | OpenAIRE |
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