Growth inhibition of human ovarian cancer cells by differential modulation of protein Kinase a Isozymes

Abstract

We examined the effect of modulation of PKA isozymes on the growth of human ovarian cancer cells. Three ovarian cancer cell lines, 2774, SK‐OV‐3, and OVCAR‐3, were examined in this study. The treatment of 5 μM 8‐CI‐cAMP, which has been known to down‐regulate RI (or type I PKA) and up‐regulate RII (or type II PKA), markedly inhibited the growth of all cell lines (50–80% at day 6). To test whether alteration in PKA regulatory subunits level can change the growth characteristics of ovarian cancer cells, we introduced RIIβ‐ expression construct and RIa antisense‐expression construct into 2774 cells. The overexpression of RIIβ down‐regulated RIa protein, and the antisense‐expression of RIα up‐regulated RIIβ protein, showing that the intracellular levels of RI and RII are reciprocally regulated. In both cases, cell growth was reduced by 30% at day 2. These results indicate that the growth of ovarian cancer cells is controlled by the signals from PKA isozymes, and the modulation of PKA isozymes can be employed f...