Antisense DNA-targeting protein kinase A-RIA subunit: a novel approach to cancer treatment.

Y. S. Cho-Chung, M. Nesterova, S. Pepe, G. R. Lee, K. Noguchi, R. K. Srivastava, A. R. Srivastava, O. Alper, Yun Gyu Park, Y. N. Lee

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

Enhanced expression of the RIa subunit of cAMP-dependent protein kinase type I (PKA-I) has been shown during carcinogenesis, in human cancer cell lines and in primary tumors. We demonstrate that the sequence-specific inhibition of RIa gene expression by antisense oligonucleotides results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin and tumors in mice. The loss of RI by the antisense results in rapid increase in the half-life of the competitor molecule, RII protein, via its stabilization in a holoenzyme complex (PKA-II) that insures depletion of PKA-I and sustained inhibition of tumor growth. RI antisense, which restrains tumor cell growth by turning on the signals for blockade of tumor cell survival, namely blockade of the tyrosine kinase signaling, cell cycle deregulation and apoptosis, provides a single gene-targeting approach to treatment of cancer.

Original languageEnglish
JournalFrontiers in bioscience : a journal and virtual library
Volume4
Publication statusPublished - 1999 Jan 1
Externally publishedYes

Fingerprint

Antisense DNA
Oncology
Cyclic AMP-Dependent Protein Kinases
Tumors
Cells
Neoplasms
Cell signaling
Holoenzymes
Deregulation
Antisense Oligonucleotides
Cell growth
Gene expression
Growth
Protein-Tyrosine Kinases
Protein Kinases
Stabilization
Genes
Gene Targeting
Apoptosis
Molecules

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Cho-Chung, Y. S., Nesterova, M., Pepe, S., Lee, G. R., Noguchi, K., Srivastava, R. K., ... Lee, Y. N. (1999). Antisense DNA-targeting protein kinase A-RIA subunit: a novel approach to cancer treatment. Frontiers in bioscience : a journal and virtual library, 4.

Antisense DNA-targeting protein kinase A-RIA subunit : a novel approach to cancer treatment. / Cho-Chung, Y. S.; Nesterova, M.; Pepe, S.; Lee, G. R.; Noguchi, K.; Srivastava, R. K.; Srivastava, A. R.; Alper, O.; Park, Yun Gyu; Lee, Y. N.

In: Frontiers in bioscience : a journal and virtual library, Vol. 4, 01.01.1999.

Research output: Contribution to journalReview article

Cho-Chung, YS, Nesterova, M, Pepe, S, Lee, GR, Noguchi, K, Srivastava, RK, Srivastava, AR, Alper, O, Park, YG & Lee, YN 1999, 'Antisense DNA-targeting protein kinase A-RIA subunit: a novel approach to cancer treatment.', Frontiers in bioscience : a journal and virtual library, vol. 4.
Cho-Chung, Y. S. ; Nesterova, M. ; Pepe, S. ; Lee, G. R. ; Noguchi, K. ; Srivastava, R. K. ; Srivastava, A. R. ; Alper, O. ; Park, Yun Gyu ; Lee, Y. N. / Antisense DNA-targeting protein kinase A-RIA subunit : a novel approach to cancer treatment. In: Frontiers in bioscience : a journal and virtual library. 1999 ; Vol. 4.
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