GROWTH-FACTOR STARVATION OF BCL-2 OVEREXPRESSING MURINE BONE-MARROW CELLS INDUCED REFRACTORINESS TO IL-3 STIMULATION OF PROLIFERATION

Murine bone-marrow derived BAF3 cells, overexpressing the human Bcl-2 gene product, showed considerably delayed onset of apoptosis when depr ived of IL-3. Such Bcl-2-BAF3 cells arrested rapidly in the G1 phase o f the cell cycle upon IL-3 removal, then became refractory to IL-3 re- stimulation. The delay in IL-3 induced proliferation of Bcl-2 over-exp ressing cells was due to down-regulation of a specific signalling path way. In the refractory cells, IL-3 was able to stimulate protein tyros ine phosphorylation and c-myc mRNA accumulation, but not rapid Erk2 ac tivation or cdc2 mRNA accumulation.