Abstract:
: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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Gordan JD,Bertout JA,Hu CJ,Diehl JA,Simon MCdoi
10.1016/j.ccr.2007.02.006subject
Has Abstractpub_date
2007-04-01 00:00:00pages
335-47issue
4eissn
1535-6108issn
1878-3686pii
S1535-6108(07)00059-1journal_volume
11pub_type
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