HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity.

Authors:
John D Gordan
John D Gordan
University of California
Berkeley | United States
Jessica A Bertout
Jessica A Bertout
University of Pennsylvania
United States
Dr. Cheng-Jun Hu, PhD
Dr. Cheng-Jun Hu, PhD
University of Colorado
Associate Professor
Pulmonary hypertension
Aurora, CO | United States

Cancer Cell 2007 Apr;11(4):335-47

Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA.

HIF-2alpha promotes von Hippel-Lindau (VHL)-deficient renal clear cell carcinoma (RCC) tumorigenesis, while HIF-1alpha inhibits RCC growth. As HIF-1alpha antagonizes c-Myc function, we hypothesized that HIF-2alpha might enhance c-Myc activity. We demonstrate here that HIF-2alpha promotes cell-cycle progression in hypoxic RCCs and multiple other cell lines. This correlates with enhanced c-Myc promoter binding, transcriptional effects on both activated and repressed target genes, and interactions with Sp1, Miz1, and Max. Finally, HIF-2alpha augments c-Myc transformation of primary mouse embryo fibroblasts (MEFs). Enhanced c-Myc activity likely contributes to HIF-2alpha-mediated neoplastic progression following loss of the VHL tumor suppressor and influences the behavior of hypoxic tumor cells.

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http://dx.doi.org/10.1016/j.ccr.2007.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145406PMC
April 2007
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272 Citations
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