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.

Keywords

AngiogenesisThrombospondin 1ThrombospondinTransfectionAngiogenesis inhibitorPhenotypeBiologyCancer researchEndogenySuppressorGeneFibroblastWild typeCell biologyChemistryGeneticsIn vitroEndocrinology

MeSH Terms

AllelesCellsCulturedFibroblastsGene Expression RegulationGenesp53HumansLi-Fraumeni SyndromeMembrane GlycoproteinsNeovascularizationPathologicPhenotypePromoter RegionsGeneticThrombospondinsTransfection

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Publication Info

Year: 1994
Type: article
Volume: 265
Issue: 5178
Pages: 1582-1584
Citations: 1446
Access: Closed

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APA Style

                            
                                
                                    Kristina M. Dameron, 
                                
                                    Olga V. Volpert, 
                                
                                    Michael A. Tainsky
                                
                                et al.
                            
                            (1994). 
                            Control of Angiogenesis in Fibroblasts by p53 Regulation of Thrombospondin-1. 
                            Science
                            , 265
                            (5178)
                            , 1582-1584.
                            https://doi.org/10.1126/science.7521539
                        

Identifiers

DOI: 10.1126/science.7521539
PMID: 7521539

Data Quality

Data completeness: 81%