title: Suppression of apoptosis by bcl-2 does not prevent p53-mediated control of experimental metastasis and anchorage dependence.
abstract: Mutations in the p53 tumor suppressor gene are frequently associated with the metastatic stage of tumor progression. Inactivation of p53 was shown to promote metastasis under experimental conditions. To determine the p53 functions that are involved in the control of tumor metastasis, we compared properties of three types of transformed mouse fibroblasts: with intact p53, with p53-mediated apoptosis suppressed by bcl-2 and with p53 inactivated by dominant negative mutants. Although expression of bcl-2 blocked apoptosis in detached cells and increased tumor cell survival in the blood circulation, it was insufficient to affect the ability of p53 to cause cell cycle arrest in detached cells and suppress experimental metastasis. For the suppression of metastasis complete inactivation of p53 was required. We conclude that the apoptotic function of p53 is dispensable for the p53-dependent suppression of experimental metastasis that is presumably achieved by controlling anchorage dependence. These data provide a possible explanation to dramatic differences in values of bcl-2 and mutant p53 as prognostic markers in human cancer.
authors.affiliation: Department of Genetics, University of Illinois at Chicago, 60607-7170, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Nikiforov
authors.forename: S S
authors.initials: SS
authors.lastname: Kwek
authors.forename: R
authors.initials: R
authors.lastname: Mehta
authors.forename: J E
authors.initials: JE
authors.lastname: Artwohl
authors.forename: S W
authors.initials: SW
authors.lastname: Lowe
authors.forename: T D
authors.initials: TD
authors.lastname: Gupta
authors.forename: G I
authors.initials: GI
authors.lastname: Deichman
authors.forename: A V
authors.initials: AV
authors.lastname: Gudkov
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D002448:Cell Adhesion; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000235:genetics; D005347:Fibroblasts; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2 / Q000235:genetics / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology