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 r esponse to DNA damage. We show that p53 acts as potent tumor-suppresso r gene independent of its well-documented effects on tumor-cell prolif eration and apoptosis. p53 activates target genes in a murine fibrosar coma cell-line but does not affect tumor cell-cycle progression or sur vival. Exogenous expression of wt-p53 does, however, block the angioge nic potential of the tumor cells resulting in formation of dormant tum ors 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 b ut not in vitro; (3) p53-gene therapy which alters a tumors angiogenic potential, can revert tumors to a dormant phenotype.