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

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 Cell

journal_title

Cancer cell

authors

Gordan JD,Bertout JA,Hu CJ,Diehl JA,Simon MC

doi

10.1016/j.ccr.2007.02.006

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

335-47

issue

4

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(07)00059-1

journal_volume

11

pub_type

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