Protein Kinase A-Directed Antisense Restrains Cancer Growth: Sequence-Specific Inhibition of Gene Expression

Abstract

Increased expression of the RI_α subunit of cAMP-dependent protein kinase type I has been shown in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. The sequence-specific inhibition of RI_α gene expression by an antisense oligodeoxynucleotide results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin. A single-injection RI_α antisense treatment in vivo also causes a reduction in RI_α expression and inhibition of tumor growth. Tumor cells behave like untransformed cells by making less protein kinase type I. The RI_α antisense, which produces a biochemical imprint for growth control, requires infrequent dosing to restrain neoplastic growth in vivo.