title: Mutant p53 facilitates pro-angiogenic, hyperproliferative phenotype in response to chronic relative hypoxia.
abstract: 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-1alpha levels in response to CRH. In addition, we found increased HIF-mediated transactivation and increased VEGF release with decreased HIF-1alpha/p53 and HIF-1alpha/MDM-2 partnering in p53-MUT versus p53-WT cells in response to CRH.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, 726 BMSB, 940 S.L. Young Boulevard, Oklahoma City, OK, USA.
authors.forename: Chandrashekhar D
authors.initials: CD
authors.lastname: Kamat
authors.forename: Dixy E
authors.initials: DE
authors.lastname: Green
authors.forename: Linda
authors.initials: L
authors.lastname: Warnke
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Thorpe
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ihnat
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009154:Mutation; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000494:pharmacology; D010641:Phenotype; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D010100:Oxygen