Mutant p53 facilitates pro-angiogenic, hyperproliferative phenotype in response to chronic relative hypoxia

There is much controversy in the literature regarding the role of p53 status response on hypoxia inducible factor (HIF) signaling in response to chronic relative hypoxia (CRH). The goal of this paper was to methodically examine this response in isogenically matched tumor cells. We report that p53-mutant (MUT) cells, versus p53-wild-type (WT) cells, showed decreased apoptosis, increased cell proliferation with higher basal HIF-1 alpha levels in response to CRH. In addition, we found increased HIF-mediated transactivation and increased VEGF release with decreased HIF-1 alpha/p53 and HIF-1 alpha/ MDM-2 partnering in p53-MUT versus p53-WT cells in response to CRH. (c) 2006 Elsevier Ireland Ltd. All rights reserved.