Science, Vol 265, Issue 5178, 1582-1584
Copyright © 1994 by American Association for the Advancement of Science
Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1
KM Dameron,
OV Volpert,
MA Tainsky,
and
N Bouck
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611.
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.
