Regulation of bcl-2 protein expression by c-myc protein in HL-60 cells during the induction of differentiation-associated apoptosis

Oncogene products, c-myc and bcl-2 protein, play an important role in the decision of the fate of cells, such as proliferation, differentiation and apoptosis. Terminally differentiated HL-60 human leukemia cells express low levels of both c-myc and bcl-2 protein, and die by apoptosis. We have previously reported that down-regulation of c-myc protein was sufficient for the induction of apoptosis in HL-60 cells, while down-regulation of bcl-2 protein was not the case. To understand regulatory mechanism between c-myc and bcl-2 protein expression, we examined the effects of c-myc or bcl-2 antisense oligonucleotides on the expression levels of bcl-2 or c-myc protein, respectively. Our experiments showed that c-myc antisense down-regulated bcl-2 protein expression, whereas bcl-2 antisense did not change the levels of c-myc protein expression. These results suggest that bcl-2 protein is regulated sequentially at downstream of the decrease in c-myc protein expression during the process of differentiation induction program. Our study identified c-myc protein as a possible primary candidate rather than bcl-2 in the gene targeting therapy of leukemia.