Abstract 989: Profiling the expression of SGLT1 in prostate cancer

Abstract Upregulation of the epidermal growth factor receptor (EGFR; HER1; erbB1), a receptor tyrosine kinase, has been linked with increased cell proliferation and decreased apoptosis and thus, with poor prognosis for cancer patients. EGFR has been found to be over-active in most tumors of epithelial origin including: non-small cell lung cancer, breast, head and neck, gastric, colorectal, esophageal, prostate, bladder, renal, pancreatic, and ovarian cancers. EGFR is elevated in prostate cancer cells along disease progression. EGFR tyrosine kinase inhibitors failed to show beneficial effects for prostate cancer patients. Previous studies have found EGFR has kinase independent prosurvival functions. Independent of its kinase activity, EGFR participates in the maintenance of the basal intracellular glucose level of cancer cells by interacting with and stabilizing SGLT1, thus preventing cancer cells from autophagic death. EGFR and SGLT1 do physically interact; however, it was previously unknown whether SGLT1 expression is upregulated along prostate cancer progression. Sodium-dependent glucose co-transporters (SGLTs) are transmemebrane glucose transporter proteins involved in the active transport of glucose. An antibody against human SGLT1 was made and used with immunohistochemistry to show in this preliminary study that SGLT1 is exclusively expressed in the hyperplastic and malignant prostate epithelial cells. SGLT1 was not expressed in the normal epithelial or BPH cells. The results from this study indicate that as the disease progresses, the increased need for glucose within the cells is at least in part being met by the continuous activity of the sodium-dependent glucose co-transporter 1. This potential role of SGLT1 in prostate cancer may provide avenues for new prostate cancer treatments. Future endeavors will focus on designing interfering peptides that ideally will interfere with the SGLT1/EGFR binding, destabilizing SGLT1 in prostate cancer cells, and promoting cell death of prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 989. doi:10.1158/1538-7445.AM2011-989