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.
|Number of pages||5|
|Publication status||Published - Feb 15 1993|
ASJC Scopus subject areas
- Cancer Research