SUPPRESSION OF APOPTOSIS BY BCL-2 DOES NOT PREVENT P53-MEDIATED CONTROL OF EXPERIMENTAL METASTASIS AND ANCHORAGE DEPENDENCE

Mutations in the p53 tumor suppressor gene are frequently associated w ith the metastatic stage of tumor progression, Inactivation of p53 was shown to promote metastasis under experimental conditions, To determi ne the p53 functions that are involved in the control of tumor metasta sis, we compared properties of three types of transformed mouse fibrob lasts: with intact p53, with p53-mediated apoptosis suppressed by bcl- 2 and with p53 inactivated by dominant negative mutants, Although expr ession of bcl-2 blocked apoptosis in detached cells and increased tumo r cell survival in the blood circulation, it was insufficient to affec t the ability of p53 to cause cell cycle arrest in detached cells and suppress experimental metastasis. For the suppression of metastasis co mplete inactivation of p53 was required, We conclude that the apoptoti c function of p53 is dispensable for the p53-dependent suppression of experimental metastasis that is presumably achieved by controlling anc horage dependence, These data provide a possible explanation to dramat ic differences in values of bcl-2 and mutant p53 as prognostic markers in human cancer.