Retroviral transduction of hematopoietic progenitor cells with mutant p53 promotes survival and proliferation, modifies differentiation potential and inhibits apoptosis.
Mutations in the p53 tumor suppressor gene have been shown to be associated with many human tumors and various leukemias and lymphomas. To examine whether constitutive overexpression of mutant p53 can effect transformation of normal hematopoietic cells, a mutant p53 gene was introduced into normal murine bone marrow hematopoietic cells by retroviral gene transfer. Compared to vector alone-infected cells, hematopoietic progenitor cells transduced with mutant p53 showed increased proliferative potential, enhanced cloning efficiencies and a modified differentiation pattern in vitro. In addition, mutant p53-transduced hematopoietic cells were more resistant to loss of viability and/or induction of apoptosis when cultured in a low concentration of serum or in the absence of both growth factors and serum. These effects occurred rapidly with no apparent contributory secondary events. No permanent cell lines or growth factor-independent cell strains were obtained. The results indicate that introduction of mutant p53 into normal hematopoietic cells in vitro contributes to transformation, including enhanced proliferative potential, modified differentiation and the suppression of apoptosis in these cells.
Shounan
Y
Y
RW Johnson Pharmaceutical Research Institute, Sydney, Australia.
Dolnikov
A
A
MacKenzie
K L
KL
Miller
M
M
Chan
Y Y
YY
Symonds
G
G
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D005260:Female; D018014:Gene Transfer Techniques; D016158:Genes, p53; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D012190:Retroviridae / Q000235:genetics*