Overexpression of human Glutamine transporters in rat liver epithelial cells provides insights into their role in cell growth and potential pharmacological inhibition as cancer targets
Bode, Barrie P.
M.S. (Master of Science)
Department of Biological Sciences
Oncology; Cytology; Molecular biology; Biology
The amino acid Glutamine not only serves several important metabolic and physiological roles in the body, but is also a coveted substrate that drives the growth of tumors. Unlike normal liver cells (hepatocytes) that transport glutamine through "System N" (SNAT3, SNAT 5), human hepatoma cells (liver cancer cells) take up glutamine several times faster through transporters distinct from System N, such as System ASC (e.g. ASCT2) and System B⁰'⁺ (e.g. ATB⁰'⁺). Previous studies have implicated these transporters in driving a wide variety of human cancers and have also shown that silencing these transporters, especially ASCT2, lead to apoptosis and inhibited cell proliferation. This study was aimed at over-expressing ASCT2 and ATB⁰'⁺ transporters in Rat Liver Epithelial cells (RLE) to screen potential pharmacological inhibitors and study the effect of over-expression on cell growth and proliferation. Results show that over-expression of these transporters did not manifest into higher growth rates and failed to provide the cells with any advantage in glutamine deprived conditions. While small molecular inhibitors like glutaminyl-paranitroanilide (GPNA) displayed selective inhibitory effects toward glutamine transport and ASCT2, they were not specific, and exerted only marginal effects on amino acid accumulation in the presence of normal compliments of amino acid substrates. Alpha-(methylamino) isobutyric acid (MeAIB) displayed no substantial effect on the transport activity indicating negligible role of System A transporters in glutamine import.
Agarwal, Aparna, "Overexpression of human Glutamine transporters in rat liver epithelial cells provides insights into their role in cell growth and potential pharmacological inhibition as cancer targets" (2017). Graduate Research Theses & Dissertations. 4236.
vi, 54 pages
Northern Illinois University
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Advisors: Barrie P. Bode.||Committee members: Sherine Elsawa; Yanbin Yin.||Includes bibliographical references.||Includes illustrations.