IMR Press / FBL / Volume 4 / Issue 4 / DOI: 10.2741/cho-chung

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Antisense DNA-targeting protein kinase A-RIA subunit: a novel approach to cancer treatment
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1 Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892, USA
Academic Editor:Eric Wickstrom
Front. Biosci. (Landmark Ed) 1999, 4(4), 898–907; https://doi.org/10.2741/cho-chung
Published: 1 December 1999
(This article belongs to the Special Issue Anti-sense therapeutics)
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.

Keywords
Antisense
Oligonucleotide
cAMP-dependent protein kinase
Cancer cells
growth inhibition
apoptosis
cell cycle deregulation
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