title: Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1.
abstract: As normal cells progress toward malignancy, they must switch to an angiogenic phenotype to attract the nourishing vasculature that they depend on for their growth. In cultured fibroblasts from Li-Fraumeni patients, this switch was found to coincide with loss of the wild-type allele of the p53 tumor suppressor gene and to be the result of reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis. Transfection assays revealed that p53 can stimulate the endogenous TSP-1 gene and positively regulate TSP-1 promoter sequences. These data indicate that, in fibroblasts, wild-type p53 inhibits angiogenesis through regulation of TSP-1 synthesis.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611.
authors.forename: K M
authors.initials: KM
authors.lastname: Dameron
authors.forename: O V
authors.initials: OV
authors.lastname: Volpert
authors.forename: M A
authors.initials: MA
authors.lastname: Tainsky
authors.forename: N
authors.initials: N
authors.lastname: Bouck
mesh_terms: D000483:Alleles; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D016158:Genes, p53; D006801:Humans; D016864:Li-Fraumeni Syndrome; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D009389:Neovascularization, Pathologic; D010641:Phenotype; D011401:Promoter Regions, Genetic; D019699:Thrombospondins; D014162:Transfection
chemical_list: D008562:Membrane Glycoproteins; D019699:Thrombospondins