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- W2808893931 abstract "// Yamhilette Licon-Munoz 1 , Colleen A. Fordyce 1 , Summer Raines Hayek 1 and Karlett J. Parra 1 1 Department of Biochemistry and Molecular Biology, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, 87131, USA Correspondence to: Karlett J. Parra, email: kjparra@salud.unm.edu Keywords: prostate cancer; androgen receptor; V-ATPase; concanamycin; HIF-1α Received: January 11, 2018 Accepted: June 04, 2018 Published: June 22, 2018 ABSTRACT Prostate Cancer (PCa) is the most commonly diagnosed cancer and the third leading cause of death for men in the United States. Suppression of androgen receptor (AR) expression is a desirable mechanism to manage PCa. Our studies showed that AR expression was reduced in LAPC4 and LNCaP PCa cell lines treated with nanomolar concentrations of the V-ATPase inhibitor concanamycin A (CCA). This treatment decreased PSA mRNA levels, indicative of reduced AR activity. V-ATPase-dependent repression of AR expression was linked to defective endo-lysosomal pH regulation and reduced AR expression at the transcriptional level. CCA treatment increased the protein level and nuclear localization of the alpha subunit of the transcription factor HIF-1 (HIF-1α) in PCa cells via decreased hydroxylation and degradation of HIF-1α. The addition of iron (III) citrate restored HIF-1α hydroxylation and decreased total HIF-1α levels in PCa cells treated with CCA. Moreover, iron treatment partially rescued CCA-mediated AR repression. Dimethyloxalylglycine (DMOG), which prevents HIF-1α degradation independently of V-ATPase, also decreased AR levels, supporting our hypothesis that HIF-1α serves as a downstream mediator in the V-ATPase-AR axis. We propose a new V-ATPase-dependent mechanism to inhibit androgen receptor expression in prostate cancer cells involving defective endosomal trafficking of iron and the inhibition of HIF-1 α-subunit turnover." @default.
- W2808893931 created "2018-06-29" @default.
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- W2808893931 date "2018-06-22" @default.
- W2808893931 modified "2023-10-18" @default.
- W2808893931 title "V-ATPase-dependent repression of androgen receptor in prostate cancer cells" @default.
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- W2808893931 doi "https://doi.org/10.18632/oncotarget.25641" @default.
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