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Protein kinase A-Iα subunit-directed antisense inhibition of ovarian cancer cell growth: crosstalk with tyrosine kinase signaling pathway

Oncogene volume 18, pages 4999–5004 (1999)Cite this article

Abstract

Expression of the RIα subunit of cAMP-dependent protein kinase type I is increased in human cancers in which an autocrine pathway for epidermal growth factor-related growth factors is activated. We have investigated the effect of sequence-specific inhibition of RIα gene expression on ovarian cancer cell growth. We report that RIα antisense treatment results in a reduction in RIα expression and protein kinase A type I, and inhibition of cell growth. The growth inhibition was accompanied by changes in cell morphology and appearance of apoptotic nuclei. In addition, EGF receptor, c-erbB-2 and c-erbB-3 levels were reduced, and the basal and EGF-stimulated mitogen-activated protein kinase activities were reduced. Protein kinase A type I and EGF receptor levels were also reduced in cells overexpressing EGF receptor antisense cDNA. These results suggest that the antisense depletion of RIα leads to blockade of both the serine-threonine kinase and the tyrosine kinase signaling pathways resulting in arrest of ovarian cancer cell growth.

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Acknowledgements

We thank Dr Sudhir Agrawal (Hybridon, Inc., Milford, MA, USA) for providing the oligonucleotides and Dr Joyce Pegues (FDA, Bethesda, MD, USA) for her kind help in the construction of EGF-receptor expression vectors. This research was supported in part by a grant from the Gynaecological Cancer Fund of the Royal Hospital Foundation.

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Author notes

  1. Özge Alper

    Present address: Ovarian Cancer Project, Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, NSW 2010, Australia

Authors and Affiliations

  1. Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, Maryland, USA

    Özge Alper & Yoon S Cho-Chung

  2. Gynaecological Cancer Center, Royal Hospital for Women, Barker Street, Randwick, NSW 2031, Australia

    Neville F Hacker

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  1. Özge Alper
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Alper, Ö., Hacker, N. & Cho-Chung, Y. Protein kinase A-Iα subunit-directed antisense inhibition of ovarian cancer cell growth: crosstalk with tyrosine kinase signaling pathway. Oncogene 18, 4999–5004 (1999). https://doi.org/10.1038/sj.onc.1202830

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