The Apoptosis Repressor with a CARD Domain (ARC) Gene Is a Direct Hypoxia-Inducible Factor 1 Target Gene and Promotes Survival and Proliferation of VHL-Deficient Renal Cancer Cells
Olga V Razorenova, Laura Castellini, Renata Colavitti, Laura E Edgington, Monica Nicolau, Xin Huang, Barbara Bedogni, Edward M Mills, Matthew Bogyo, Amato J Giaccia
MOLECULAR AND CELLULAR BIOLOGY | AMER SOC MICROBIOLOGY | Published : 2014
The induction of hypoxia-inducible factors (HIFs) is essential for the adaptation of tumor cells to a low-oxygen environment. We found that the expression of the apoptosis inhibitor ARC (apoptosis repressor with a CARD domain) was induced by hypoxia in a variety of cancer cell types, and its induction is primarily HIF1 dependent. Chromatin immunoprecipitation (ChIP) and reporter assays also indicate that the ARC gene is regulated by direct binding of HIF1 to a hypoxia response element (HRE) located at bp -190 upstream of the transcription start site. HIFs play an essential role in the pathogenesis of renal cell carcinoma (RCC) under normoxic conditions, through the loss of the Von Hippel-Lin..View full abstract
Awarded by NCI/NIH grants
Awarded by NATIONAL CANCER INSTITUTE
Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
This work was supported by a gift from the Silicon Valley Community Foundation (A.J.G.) and NCI/NIH grants CA-67166 (A.J.G.), CA-088480 (A.J.G.), and T32 CA121940 (O.V.R.).