Abstract
Abstract Organic anion transporting polypeptides (OATPs) are membrane transporters that facilitate the movement of large substrates into cells. One family member, organic anion transporting polypeptide 1B3 (OATP1B3) is aberrantly overexpressed in prostate cancer and has been shown to influx both endogenous small molecules and chemotherapy reagents. Our hypothesis is that the OATP1B3 affects tumor growth by influxing testosterone. However, little is known about the cause of OATP1B3 expression in cancer and the impact of OATP1B3 transport on tumor growth. Therefore, we completed a study investigating putative hypoxia elements in the OATP1B3 promoter region, characterizing the impact of OATP1B3 androgen transport on prostate cancer growth, and examining the effect of OATP1B3 on the efficacy of standard prostate cancer treatments. The results showed that OATP1B3 co-localized with HIF 1-alpha in prostate cancer tissues from patients, correlated significantly to HIF1A in xenograft tumors under castration (P=0.005), and confirmed HIF-1alpha elements in the SLCO1B3 promoter region. In addition, radioactive transport assays with Xenopus oocytes showed that OATP1B3 transports testosterone and dihydrotestosterone 50- to 250-fold over passive diffusion at low physiological concentrations. A prostate cancer cell line expressing OATP1B3 grew faster than untransfected in response to androgens at all concentrations. Finally, OATP1B3 increased cell sensitivity to docetaxel treatment. In summary, these data show that hypoxia and castration increases OATP1B3 expression in cancer, OATP1B3-mediated androgen transport significantly impacts prostate cancer growth and OATP1B3 impacts the efficacy of docetaxel. These data provides evidence that OATP1B3 impacts prostate cancer growth and treatment. Future studies could screen for specific inhibitors of OATP1B3-mediated androgen transport. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1848. doi:1538-7445.AM2012-1848
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