ProfIling the Expression of SGLTI in Prostate Cancer
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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 any beneficial effects for prostate cancer patients. Previous studies had found that independent of its kinase activity, EGFR still stimulated DNA synthesis and cell survival. Separately, it is known that 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 SGL Tl, thus preventing cancer cells from autophagic death. EGFR and SGLTI do physically interact; however, it was previously unknown whether SGL Tl expression is upregulated along prostate cancer progression. An antibody against human SGLTI was purified from serum and used with immunohistochemistry to show in this preliminary study that SGLTI is exclusively expressed by the hyperplastic and malignant prostate epithelial cells. Future endeavors will focus on designing interfering peptides that ideally will interfere with the SGLTl/EGFR binding, destabilizing SGLTI in prostate cancer cells, and allowing apoptosis to occur via glucose starvation.