p53 induces angiogenesis-restricted dormancy in a mouse fibrosarcoma.
The p53 tumor-suppressor gene is inactivated in over 50% of all human cancers. In normal cells, p53 induces growth arrest and apoptosis in response to DNA damage. We show that p53 acts as potent tumor-suppressor gene independent of its well-documented effects on tumor-cell proliferation and apoptosis. p53 activates target genes in a murine fibrosarcoma cell-line but does not affect tumor cell-cycle progression or survival. Exogenous expression of wt-p53 does, however, block the angiogenic potential of the tumor cells resulting in formation of dormant tumors in vivo. These data provide evidence that: (1) p53 acts as a tumor suppressor gene independent of its anti-proliferative effects; (2) By inhibiting angiogenesis p53 can indirectly induce apoptosis in vivo but not in vitro; (3) p53-gene therapy which alters a tumors angiogenic potential, can revert tumors to a dormant phenotype.
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
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L
Holmgren
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G
Jackson
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J
Arbiser
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005354:Fibrosarcoma / Q000098:blood supply* / Q000473:pathology* / Q000556:secondary; D016158:Genes, p53; D015316:Genetic Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured