p53-independent tumor growth and in vitro cell survival for F-MuLV-induced erythroleukemias.
Retroviral insertional activation of the Fli-1 proto-oncogene is the first genetic event associated with the induction of erythroleukemias by the Friend murine leukemia virus (F-MuLV). Mutations within p53, which are only detected in cell lines established from transplanted tumors, have been previously shown to be associated with the immortalization of erythroleukemic cells in culture. In this study, we have demonstrated that primary erythroleukemic cells grown in liquid culture undergo rapid apoptosis independent of the stabilization of wild-type p53 protein. Further confirmation that the programmed cell death observed for liquid-cultured F-MuLV-induced primary erythroleukemic cells is largely p53 independent was provided by experimentation with a transgenic mouse line containing multiple copies of the dominant negative mutant p53Pro-193 allele. Erythroleukemic cells taken from tumor-bearing transgenic mice expressing high levels of the mutant p53Pro-193 undergo programmed cell death in culture in a manner that is largely identical to that observed for tumor cells derived from nontransgenic littermates. Furthermore, the rate of development of F-MuLV-induced erythroleukemias for both p53Pro-193-transgenic and nontransgenic littermates are similar. Moreover, cytogenetic analysis indicates that primary erythroleukemia cells are diploid, whereas chromosomal aberrations were observed in all established cell lines. These results are consistent with the notion that mutations within the p53 tumor suppressor gene affect genomic stability, subsequently leading to changes in gene expression that are associated with the immortalization of erythroid progenitor cells.
Howard
J
J
Division of Cancer Biology Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
Ung
Y
Y
Adachi
D
D
Ben-David
Y
Y
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005622:Friend murine leukemia virus / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D007621:Karyotyping; D004915:Leukemia, Erythroblastic, Acute; D007942:Leukemia, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009929:Organ Size; D012192:Retroviridae Infections; D013154:Spleen; D019076:Transgenes / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000502:physiology / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014412:Tumor Virus Infections
D016159:Tumor Suppressor Protein p53