Profiling the Expression of SGLT1 in Prostate Cancer

Abstract

Current therapies of prostate cancer, the most frequently diagnosed cancer, are often ineffective and cause serious adverse effects.1 Upregulation of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, has been linked with increased cell proliferation and decreased apoptosis.2 EGFR is elevated in prostate cancer cells along disease progression.2 EGFR tyrosine kinase inhibitors failed to show any beneficial effects for prostate cancer patients.3 Independent of its kinase activity, EGFR still stimulated DNA synthesis and cell survival.4 Two different processes mediate cellular uptake of glucose: a facilitated transport mechanism and an active transport that is both energy and sodium dependent. Sodium-dependent glucose co-transporters (SGLTs) are transmemebrane glucose transporter proteins involved in the active transport of glucose. 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.5 EGFR and SGLT1 do physically interact; however, it was previously unknown whether SGLT1 expression is upregulated along prostate cancer progression. The levels of SGLT1 expression correlated with malignant progression of prostate cancer. SGLT1 was not expressed in the normal or BPH cells, but only in the hyperplastic and malignant prostate epithelial cells. The results 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 SGLT1s.