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, over-expressing the human Bcl-2 gene product, showed considerably delayed onset of apoptosis when deprived of IL-3. Such Bcl-2-BAF3 cells arrested rapidly in the G1 phase of 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-expressing cells was due to down-regulation of a specific signalling pathway. In the refractory cells, IL-3 was able to stimulate protein tyrosine phosphorylation and c-myc mRNA accumulation, but not rapid Erk2 activation or cdc2 mRNA accumulation.