Bode, Barrie P.
M.S. (Master of Science)
Department of Biological Sciences
Hypoxia represents a major driver of the cancer phenotype in solid tumors, especially those of hepatic origin. Low oxygen availability triggers a complex cellular response which alters metabolism and promotes cellular invasion. Growing evidence suggests the amino acid glutamine, an important molecular currency for both energy producing reactions and biosynthetic pathways, plays an enhanced role in cancer cells under hypoxia. Hypoxia-inducible factors (HIFs) are transcription factors crucial for regulating the cellular response to low oxygen. Family member HIF-1 has been well studied, however, recent evidence suggests HIF-2 may have a regulatory role in amino acid transport and metabolism under hypoxia. Therefore, this study generated a series of human liver cancer cell lines either lacking or overexpressing the HIF-2 alpha subunit in order to examine its potential role in cellular glutamine transport. The expression of amino acid transporters ASCT2 and LAT1 was examined under both normal and low oxygen conditions. Loss of HIF-2α resulted in a substantial decrease in ASCT2 under long term hypoxia but did not appear to impact LAT1. No change in either transporter was observed with the overexpression of HIF-2α. Results suggest HIF-2 may be necessary to maintain hypoxic expression of certain c-Myc regulated genes, possibly by countering the inhibitory effect of HIF-1. The broader role of HIF-2 on amino acid transport, including transporters not driven by myc, will require further investigation.
Misurelli, Jason A., "HIF-2 Regulation of Amino Acid Transporter Expression in Hepatocellular Carcinoma Cells" (2019). Graduate Research Theses & Dissertations. 7454.
Northern Illinois University
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