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Nuclear translocation of the catalytic subunit of protein kinase A induced by an antisense oligonucleotide directed against the RIα regulatory subunit

Oncogene volume 20, pages 8019–8024 (2001)Cite this article

Abstract

The regulatory (R) subunits of cAMP-dependent protein kinase (PKA) are implicated in the regulation of cell proliferation and differentiation. There are two isoforms of PKA that are distinguished by two types of R subunit, RI and RII. Evidence suggests that RI is associated with proliferation and RII is associated with cell differentiation. Previous work in this laboratory has demonstrated that depletion of the RIα subunit by treatment with an antisense oligonucleotide (ODN) induces differentiation in leukemia cells and growth arrest and apoptosis in epithelial cancer cells. Using the prostate cancer cell line PC3M as a model system, we have developed a cell line that overexpresses a retroviral vector construct containing the RIα antisense gene. This cell line has been characterized and the effectiveness of the construct determined. In the work presented here, we demonstrate by immunocytochemistry that treatment with RIα antisense ODN induces translocation of the Cα subunit of PKA to the nucleus of PC3M prostate cancer cells. The translocation of Cα triggered by exogenous antisense ODN treatment mirrors that observed in cells endogenously overexpressing the antisense gene. Triggering the nuclear translocation of the Cα subunit of PKA in the cell may be an important mechanism of action of RIα antisense that regulates cell growth independent of adenylate cyclase and cellular cAMP levels. The nuclear localization of the Cα subunit of PKA may be an essential step in revealing the mechanism whereby this critical kinase regulates cell growth.

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Acknowledgements

We thank Dr S Agrawal (Hybridon, Inc. Milford, MA, USA) for providing the RIα antisense oligonucleotide and the control oligonucleotide. The plasmid OT1529-RIα antisense gene was constructed by Dr Langzhu Tan, and the PC3M cell line stably transfected with the OT1529-RIα antisense gene vector was developed by Dr Yee Sook Cho, in our laboratory. Dr Frances McFarland, of Palladian Partners, Inc., provided editorial support under contract number N02-BC-76212/C2700212 with the National Cancer Institute.

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  1. Cellular Biochemistry Section, Basic Research Laboratories, The Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, Maryland, USA

    Catherine L Neary & Yoon S Cho-Chung

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  1. Catherine L Neary
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  2. Yoon S Cho-Chung
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Correspondence to Yoon S Cho-Chung.

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Neary, C., Cho-Chung, Y. Nuclear translocation of the catalytic subunit of protein kinase A induced by an antisense oligonucleotide directed against the RIα regulatory subunit. Oncogene 20, 8019–8024 (2001). https://doi.org/10.1038/sj.onc.1204992

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