Cellular Distribution of Glut-1 and Glut-5 in Benign and Malignant Human Prostate Tissue Karin Reinicke, 1 Paula Sotomayor, 2 Pedro Cisterna, 1 Carolina Delgado, 3 Francisco Nualart, 1 ** and Alejandro Godoy 4 * 1 Departamento de Biologı ´a Celular, Universidad de Concepcio ´n, Concepcio ´n, Chile 2 Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263 3 Departamento de Patologı ´a, Universidad de Concepcio ´n, Concepcio ´n, Chile 4 Department of Urology, Roswell Park Cancer Institute, Buffalo, New York 14263 ABSTRACT Over-expression of hexose transporters (Gluts), specifically Glut-1, is a common event in human malignancies. In prostate cancer (CaP), however, expression of Gluts has been characterized poorly. In this study, expression and distribution of Glut-1 and Glut-5 proteins were characterized using immunohistochemistry in 76 specimens of benign prostate, 10 specimens of high-grade intraepithelial neoplasia (HGPIN), and 28 specimens of CaP. In addition, mRNA expression of Glut-2, Glut-7, Glut-9, and Glut-11 was analyzed in a set of five specimens of benign prostate and CaP. In benign prostate, Glut-1 localized to the basal cells and to the basolateral membrane of secretory/luminal epithelial cells. Glut-5, however, localized to the apical membrane of secretory/luminal epithelial cells. In HGPIN, Glut-1 was immunohistochemically undetectable. Glut-5, however, localized to the apical membrane of the neoplastic epithelial cells. In CaP, Glut-1 and Glut-5, were immunohistochemically undetectable. However, over-expression of GLUT1 was observed in some specimens of highly proliferative intraductal CaP. Glut-7, Glut-9, and Glut-11 mRNAs were detected in benign prostate and CaP, however, only Glut-11 mRNA was consistently up-regulated in CaP compared to benign prostate. Low levels of expression of Glut-1 protein in the majority of CaP could explain, at least in part, the limited clinical applicability of positron emission tomography using 2-[18F]-fluoro-2-deoxy-D-glucose for imaging CaP. Moreover, expression of Glut-5 in HGPIN suggested that fructose could be utilized as potential metabolic substrate in HGPIN. Understanding the molecular mechanisms involved in regulation/dysregulation of Gluts in CaP could provide insight in the understanding of hexose metabolism in CaP. J. Cell. Biochem. 113: 553–562, 2012. ß 2011 Wiley Periodicals, Inc. KEY WORDS: GLUCOSE; GLUCOSE TRANSPORTER; GLUT-1; GLUT-5; PROSTATE; PROSTATE CANCER G lucose transport in human cells is mediated mostly by the mammalian facilitative hexose transporter (Glut) family. Fourteen members of the Glut family have been described: Glut-1 to Glut-12, Glut-14, and a proton-coupled myoinositol transporter (HMIT) [Joost and Thorens, 2001]. These transporters show tissue- specific expression and multifunctional transport capacity. Among all of the isoforms, only Glut-1, Glut-2, Glut-3, Glut-4, and Glut-5 have been characterized functionally in detail [Mueckler et al., 1985; Fukumoto et al., 1988, 1989; Kayano et al., 1988, 1990; Catalona et al., 1991; Nualart et al., 1999; Watanabe et al., 1999]. Glut-6, Glut-7, Glut-8, Glut-9, Glut-10, Glut-11, and Glut-12 have been identified recently using homology searches of EST databases and their function is less well understood [Nualart et al., 2009]. Glut-14 is a duplication of Glut-3 and Glut-13 corresponds to HMIT. Glut-1 has been reported to be the most ubiquitous isoform and Glut-1 transports glucose and galactose, but not fructose [Mueckler et al., 1985]. Glut-2 and Glut-5 have been reported to be the only proteins to mediate fructose transport in human cells [Fukumoto et al., 1988; Journal of Cellular Biochemistry ARTICLE Journal of Cellular Biochemistry 113:553–562 (2012) 553 Francisco Nualart and Alejandro Godoy contributed equally to this work. Grant sponsor: Fondecyt; Grant number: 1100396; Grant sponsor: DoD Post-Doctoral Training Award (A.G.); Grant number: W81XWH-08-1-0330. *Correspondence to: Alejandro Godoy, PhD, Department of Urology, Roswell Park Cancer Institute, Buffalo, NY 14263. E-mail: alejandro.godoy@roswellpark.org **Correspondence to: Francisco Nualart, PhD, Departamento de Biologı ´a Celular, Facultad de Ciencias Biolo ´ gicas, Universidad de Concepcio ´ n, Concepcio ´ n, Chile. E-mail: frnualart@udec.cl Received 12 September 2011; Accepted 14 September 2011  DOI 10.1002/jcb.23379  ß 2011 Wiley Periodicals, Inc. Published online 21 September 2011 in Wiley Online Library (wileyonlinelibrary.com).