Protein kinase A-directed antisense restrains cancer growth: sequence-specific inhibition of gene expression.
Increased expression of the RI alpha 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 alpha 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 alpha antisense treatment in vivo also causes a reduction in RI alpha expression and inhibition of tumor growth. Tumor cells behave like untransformed cells by making less protein kinase type I. The RI alpha antisense, which produces a biochemical imprint for growth control, requires infrequent dosing to restrain neoplastic growth in vivo.
Cellular Biochemistry Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA.
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Cho-Chung
D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010446:Peptide Fragments / Q000502:physiology*
D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D010446:Peptide Fragments; D017868:Cyclic AMP-Dependent Protein Kinases