An Antisense Oligodeoxynucleotide Targeted Against the Type IIβRegulatory Subunit mRNA of Protein Kinase Inhibits cAMP-Induced Differentiation in HL-60 Leukemia Cells Without Affecting Phorbol Ester Effects

The type IIβregulatory subunit of cAMP-dependent protein kinase (RIIβ) 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 RIIβantisense synthetic oligodeoxynucleotide, and the effects on cAMP-induced growth regulation were examined. Exposure of these cells to RIIβantisense 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 RIIβprotein. Exposure to RIIβsense, RIαand RIIαantisense, or irrelevant oligodeoxynucleotides had no such effect. These results show that the RIIβregulatory subunit of protein kinase plays a critical role in the cAMP-induced growth regulation of HL-60 leukemia cells.