¹Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, C.R.S., 00158 Rome, Italy

²Departement of Experimental Medicine, University of L'Aquila, 67100 L'Aquila, Italy

³Dept. of Molecular Cell Biology, The Weizmann Institute Rehovot, Israel

^aAuthor for correspondence

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.

differentiation; tumor suppression; cellular environment