|
 |
|||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||
 |
 |
|
|
Tumor Reversion: Protein Kinase A Isozyme Switching
Cellular Biochemistry Section, Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892-1750, USA
Address correspondence to: Y. S. Cho-Chung, M.D., Ph.D., Cellular Biochemistry Section, BRL, CCR, National Cancer Institute, Building 10, Room 5B05, 9000 Rockville Pike, Bethesda, MD 20892-1750. Voice: 301-496-4020; fax: 301-480-8587. yc12b{at}nih.gov
The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in the isoforms RI and RII, which distinguish PKA isozymes type I (PKA-I) and type II (PKA-II). Evidence obtained from different experimental approaches—such as site-selective cAMP analogs, antisense oligonucleotides, transcription factor decoys, cDNA microarrays, and gene transfer—has shown that PKA-I and -II are expressed in a balance of cell growth and differentiation. Loss of this balance may underlie cancer genesis and progression. DNA microarrays demonstrate that antisense suppression of the RI
 , which upregulates RIIß, downregulates a wide range of genes involved in cell proliferation and transformation while upregulating cell differentiation and reverse transformation genes in PC3M prostate tumors that undergo regression. Conversely, the vector-mediated overexpression of RIIß, as opposed to those of RI and C, exhibits induction of differentiation genes along with suppression of cell proliferation and transformation genes leading to reversion of tumor phenotype. Thus, switching of PKA isozyme can cause tumor cells to undergo phenotypic reversion of the malignancy.
Key Words: protein kinase A • antisense • gene transfer • gene therapy • site-selective cAMP analog • tumor reversion This article has been cited by other articles:
| |||||||||||||||||||||||||||||
 |
 |
