AN ANTISENSE OLIGODEOXYNUCLEOTIDE TARGETED AGAINST THE TYPE-II-BETA REGULATORY SUBUNIT MESSENGER-RNA OF PROTEIN-KINASE INHIBITS CAMP-INDUCED DIFFERENTIATION IN HL-60 LEUKEMIA-CELLS WITHOUT AFFECTING PHORBOL ESTER EFFECTS

The type II(β) regulatory subunit of cAMP-dependent protein kinase (RII(β)) has been hypothesized to play an important role in the growth inhibition and differentiation induced by site-selective cAMP analogs in human cancer cells, but direct proof of this function has been lacking. To address this issue, HL-60 human promyelocytic leukemia cells were exposed to RII(β) antisense synthetic oligodeoxynucleotide, and the effects on cAMP-induced growth regulation were examined. Exposure of these cells to RII(β) antisense oligodeoxynucleotide resulted in a decrease in cAMP analog-induced growth inhibition and differentiation without apparent effect on differentiation induced by phorbol esters. This loss in cAMP growth regulatory function correlated with a decrease in basal and induced levels of RII(β) protein. Exposure to RII(β) sense, RI(α) and RII(α) antisense, or irrelevant oligodeoxynucleotides had no such effect. These results show that the RII(β) regulatory subunit of protein kinase plays a critical role in the cAMP-induced growth regulation of HL-60 leukemia cells.