HIF-1, HIF-2 AND VHL mRNA EXPRESSION IN DIFFERENT CELL LINES UNDER HYPOXIA
1Palladin Institute of Biochemistry, National Academy of Science of Ukraine, Kyiv, Ukraine;
2National Cancer Center, Research Institute, East Kashiwa, Chiba, Japan
Hypoxia inducible factor-1 (HIF-1) mRNA expression is significantly decreased under hypoxia in different cell lines exposed directly to hypoxia or treated with dimethyloxalylglycine which mimics hypoxic effects under normoxic conditions. However, the decreased expression of HIF-1? mRNA is accompanied by an increase of HIF-1? protein (pHIF-1?) level as well as by overexpression of known HIF-dependent genes (VEGF, Glut1, PFKFB-3 and PFKFB-4) under hypoxic conditions or with the use of dimethyloxalylglycine. Expression of HIF-1? mRNA also depends on iron because desferrioxamine and cobalt chloride produce similar to hypoxia effects on the levels of this mRNA. It was shown that HIF-1? mRNA expression did not change significantly in some cell lines (SKBR3, MDA-MB468 and BT549) under hypoxia. However, in these cell lines hypoxia decreases expression of HIF-2? mRNA, another member of HIF-? gene family, as a result of cell specific regulation of HIF-? genes under hypoxia. Moreover, hypoxia slightly induces expression of PFKFB-4 mRNA in SKBR3, MDA-MB468 and BT549 as compared to other cell lines where this effect of hypoxia was much stronger and adaptation to hypoxia is controlled by HIF-1?. Hypoxia slightly reduces expression of tumor suppressor VHL which targets HIF-1? for ubiquitination. Thus, our results clearly demonstrated down regulation of HIF-1? or HIF-2? in different cell lines by hypoxia.
Key words: HIF-1, HIF-2, VHL, hypoxia, dimethyloxalylglycine.
Published at the site: 2006-09-14
The original article in Ukrainian is available for download in PDF format.
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