ProfIling the Expression of SGLTI in Prostate Cancer
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Authors
Blessing, Alicia
Issue Date
2010
Type
Thesis
Language
en_US
Keywords
Alternative Title
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 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.
Description
v, 28 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.