Wild-type p53 induces diverse effects in 32D cells expressing different oncogenes.
Expression of exogenous wild-type (wt) p53 in different leukemia cell lines can induce growth arrest, apoptotic cell death, or cell differentiation. The hematopoietic cell lines that have been used so far to study wt p53 functions have in common the characteristic of not expressing endogenous p53. However, the mechanisms involved in the transformation of these cells are different, and the cells are at different stages of tumor progression. It can be postulated that each type of neoplastic cell offers a particular environment in which p53 might generate different effects. To test this hypothesis, we introduced individual oncogenes into untransformed, interleukin-3 (IL-3)-dependent myeloid precursor 32D cells to have a single transforming agent at a time. The effects induced by wt p53 overexpression were subsequently evaluated in each oncogene-expressing 32D derivative. We found that in not fully transformed, v-ras-expressing 32D cells, as already shown for the parental 32D cells, overexpression of the wt p53 gene caused no phenotypic changes and no reduction of the proliferative rate as long as the cells were maintained in their normal culture conditions (presence of IL-3 and serum). An accelerated rate of apoptosis was observed after IL-3 withdrawal. In contrast, in transformed, IL-3-independent 32D cells, wt p53 overexpression induced different effects. The v-abl-transformed cells manifested a reduction in growth rate, while the v-src-transformed cells underwent monocytic differentiation. These results show that the phenotype effects of wt p53 action(s) can vary as a function of the cellular environment.
Soddu
S
S
Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, CRS, Rome, Italy.
Blandino
G
G
Scardigli
R
R
Martinelli
R
R
Rizzo
M G
MG
Crescenzi
M
M
Sacchi
A
A
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000502:physiology; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis / Q000235:genetics; D015688:Oncogene Protein pp60(v-src) / Q000096:biosynthesis / Q000235:genetics; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016374:Oncogene Proteins v-abl / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D007377:Interleukin-3; D015513:Oncogene Proteins; D016374:Oncogene Proteins v-abl; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D015688:Oncogene Protein pp60(v-src); D015689:Oncogene Protein p21(ras)