A single-injection protein kinase A-directed antisense treatment to inhibit tumour growth.
Expression of the RI alpha subunit of cAMP-dependent protein kinase type I is enhanced in human cancer cell lines, in primary tumours, in cells after transformation and in cells upon stimulation of growth. We have investigated the effect of sequence-specific inhibition of RI alpha gene expression on in vivo tumour growth. We report that single injection RI alpha antisense treatment results in a reduction in RI alpha expression and inhibition of tumour growth. Tumour cells behaved 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 halt neoplastic growth in vivo.
Nesterova
M
M
Cellular Biochemistry Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1750, USA.
Cho-Chung
Y S
YS
D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000473:pathology / Q000628:therapy*; D002472:Cell Transformation, Viral; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D015316:Genetic Therapy; D006801:Humans; D007279:Injections, Subcutaneous; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D007527:Isoenzymes; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D017868:Cyclic AMP-Dependent Protein Kinases