Antisense protein kinase A RI alpha-induced tumor reversion: portrait of a microarray.
Antisense oligonucleotides can selectively block disease-causing genes due to the specificity of the Watson-Crick base-pairing mechanism of action. A genome-wide view of antisense technology is illustrated via protein kinase A RI alpha antisense. Complementary DNA microarray analysis of the RI alpha antisense-induced expression profile shows the up- and down-regulation of clusters of coordinately expressed genes that define the molecular portrait of a reverted tumor cell phenotype. This global view broadens the horizons of antisense technology; it advances the promise of antisense beyond a single target gene to the whole cell and the whole organism. Along with recent rapid advances in oligonucleotide technologies-including new chemical and biological understanding of more sophisticated nucleic acid drugs-oligonucleotide-based gene silencing offers not only an exquisitely specific genetic tool for exploring basic science but also an exciting possibility for treating and preventing cancer and other diseases.
Cho-Chung
Yoon S
YS
Cellular Biochemistry Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Rockville Pike, Bethesda, MD 20892-1750, USA. ycl2b@nih.gov
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002986:Clinical Trials as Topic; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D010641:Phenotype; D015854:Up-Regulation
D000970:Antineoplastic Agents; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense; C517834:PRKAR1A protein, human; D017868:Cyclic AMP-Dependent Protein Kinases