An antisense oligodeoxynucleotide that depletes RIα subunit of cyclic AMP-dependent protein kinase induces growth inhibition in human cancer cells

Hiroshi Yokozaki, Alfredo Budillon, Giampaolo Tortora, Scott Meissner, Serge L. Beaucage, Keizaburo Miki, Yoon S. Cho-Chung

Research output: Contribution to journalArticle

Abstract

Enhanced expression of the RIα subunit of cyclic AMP-dependent protein kinase type I has been correlated with cancer cell growth. We provide evidence that RIα is a growth-inducing protein that may be essential for neoplastic cell growth. Human colon, breast, and gastric carcinoma and neuroblastoma cell lines exposed to a 21-mer human RIα antisense phosphorothioate oligodeoxynucleotide (S-oligodeoxynucleotide) exhibited growth inhibition with no sign of cytotoxicity. Mismatched sequence (random) S-oligodeoxynucleotides of the same length exhibited no effect. The growth inhibitory effect of RIα antisense oligomer correlated with a decrease in the RIα mRNA and protein levels and with an increase in RIIβ (the regulatory subunit of protein kinase type II) expression. The growth inhibition was abolished, however, when cells were exposed simultaneously to both RIα and RIIβ antisense S-oligodeoxynucleotides. The RIIβ antisense S-oligodeoxynucleotide alone, exhibiting suppression of RIIβ along with enhancement of RIα expression, led to slight stimulation of cell growth. These results demonstrate that two isoforms of cyclic AMP receptor proteins, RIα and RIIβ, are reciprocally related in the growth control of cancer cells and that the RIα antisense oligodeoxynucleotide, which efficiently depletes the growth stimulatory RIα, is a powerful biological tool toward suppression of malignancy.

Original languageEnglish
Pages (from-to)868-872
Number of pages5
JournalCancer Research
Volume53
Issue number4
Publication statusPublished - Feb 15 1993

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'An antisense oligodeoxynucleotide that depletes RIα subunit of cyclic AMP-dependent protein kinase induces growth inhibition in human cancer cells'. Together they form a unique fingerprint.

  • Cite this