Oncogenes belonging to the CSF-1 transduction pathway direct p53 tumor suppressor effects to monocytic differentiation in 32D cells.
Expression of exogenous wt-p53 in different tumor cell lines can induce growth arrest, apoptosis, or differentiation. Several experimental works have highlighted the relevance of cellular context in the determination of p53-mediated final outcomes. We recently observed that these diverse wt-p53 effects can also be induced by overexpressing wt-p53 in a single cell type-the 32D myeloid progenitors-transformed with different activated oncogenes. Here we show that 32D cells transformed with two different oncogenes, v-src or c-fms [S301,F969], both belonging to the CSF-1 transduction pathway, respond to exogenous wt-p53 expression with the same final outcome-monocytic differentiation. This result is particularly significant since 32D cells do not spontaneously express the CSF-1 receptor, whereas they undergo granulocytic differentiation upon G-CSF stimulation. These data strongly support the idea that wt-p53 suppressing effects result from interactions between p53 activity and the signaling pathways activated in different transformed cells.
Martinelli
R
R
Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, C.R.S., Rome, Italy.
Blandino
G
G
Scardigli
R
R
Crescenzi
M
M
Lombardi
D
D
Sacchi
A
A
Soddu
S
S
D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D016236:Genes, fms; D016391:Genes, src; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D007377:Interleukin-3; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor