ANTISENSE DEPLETION OF RI-ALPHA SUBUNIT OF PROTEIN-KINASE-A INDUCES APOPTOSIS AND GROWTH ARREST IN HUMAN BREAST-CANCER CELLS

In recent years, several laboratories have explored the possibility of using antisense oligodeoxynucleotides for specific manipulation of ge ne expression leading to cancer treatment. The enhanced expression of the RI alpha subunit of cyclic AMP-dependent protein kinase type I (PK A-I) has been correlated with cancer cell growth. In the present study , the effects of an antisense oligodeoxynucleotide targeted against RI alpha subunit of PKA-I on growth inhibition and apoptosis in MDA-MB-2 31 human breast cancer cells were investigated. The growth inhibitory effects of RI alpha antisense oligodeoxynucleotide correlated with a d ecrease in the RI alpha mRNA and protein levels. The growth inhibition was accompanied by changes in the cell cycle phase distribution, cell morpbology, cleavage of poly (ADP-ribose) polymerase (PARP), and appe arance of apoptotic nuclei. By comparison, mismatched control oligodeo xynucleotide had no effect. On the basis of these results, it can be s uggested that the RI alpha antisense oligodeoxynucleotide, which effic iently depletes the growth stimulatory RI alpha and induces apoptosis/ differentiation, could be used as a therapeutic agent for breast cance r treatment.