Abstract B28: Organic anion transporting polypeptide 1B3 as a novel biomarker for hypoxia in prostate cancer.

Abstract

Abstract The organic anion transporting polypeptide 1B3 (OATP1B3) is aberrantly expressed in prostate cancer. We showed that OATP1B3 expression correlated to Gleason score in primary prostate cancer samples. As a transporter, OATP1B3 functions to influx both endogenous small molecules and xenobiotics. We also demonstrated that decreased survival and decreased progression in patients with prostate cancer was associated with a polymorphism in SLCO1B3, the gene encoding OATP1B3. However, OATP1B3 has not been validated as a clinical biomarker and the cause of expression in cancer is unknown. The purpose of this study was to identify a molecular regulation that explains OATP1B3 expression in cancer. In this study, we show that hypoxia increases the transcriptional and translational expression of OATP1B3 in cancer, that hypoxia-inducible factor 1-alpha (HIF1-alpha) binds putative hypoxia response elements in the SLCO1B3 promoter region by chromatin immunoprecipitation, and show co-localization of hypoxia and OATP1B3 by immunohistochemistry in clinical tissue samples. Additionally, cooperation between androgen- and hypoxia-signaling pathways explains the increased expression of OATP1B3 in prostate cancer xenografts under castration conditions. These data provide a foundation for the use of OATP1B3 as a biomarker of cancerous disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B28.