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

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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

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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., Srivastava, A. R., Alper, O., Park, Y. G., & 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.