APOPTOSIS IN V-MYC TRANSFORMATION OF MYELOMONOCYTIC CELLS AND ITS MODULATION BY CSF-1

c-myc is a proto-oncogene essential for cell growth. When activated, i ts expression can lead to uncontrolled cell proliferation, transformat ion and tumorigenesis. The cell line tEMmyc4 is a murine myelomonocyti c cell line that was established following transformation by v-myc. It has a high level of v-myc expression and constitutively expresses end ogenous CSF-1, the monocytic growth and viability factor. Under growth restricting conditions (high cell density, serum deprivation, heat sh ock, or dexamethasone addition) cells of this line were found to under go cell death through apoptosis. The induction of apoptosis by dexamet hasone was associated with a decrease in constitutive CSF-1 expression without significant change in v-myc expression. Exogenous CSF-1 rescu ed these cells from dexamethasone induced-apoptosis. In vivo studies s howed that tEMmyc4 cells were tumorigenic in syngeneic animals despite exhibiting some spontaneous apoptosis within the tumour mass. Co-admi nistration of dexamethasone with the tumour cells significantly inhibi ted tumor development and the administration of dexamethasone to mice with established tumors resulted in tumor regression in all mice. This regression was associated with a high level of apoptosis and necrosis in the tumors. This study shows a correlation between the in vitro an d in vivo induction of apoptosis and indicates that cancer cells beari ng activated oncogenes may be more sensitive to apoptosis induction by chemotherapeutic agents.