OVEREXPRESSION OF RII-BETA REGULATORY SUBUNIT OF PROTEIN-KINASE-A INDUCES GROWTH-INHIBITION AND REVERSE-TRANSFORMATION IN SK-N-SH HUMAN NEUROBLASTOMA-CELLS

SK-N-SH human neuroblastoma cell line was employed to test whether dir ect introduction of the RII beta subunit of PKA could induce growth in hibition and reverse-transformation of cancer cells. We infected SK-N- SH cells with an RII beta expression construct and the clonal line wit h the highest expression level was selected to examine the effect of R II beta overexpression. Elevation of RII beta was accompanied by marke d reduction of RI alpha level and increase of C alpha level. Since the mRNA levels of RI alpha and C alpha were not altered by increased RII beta, the changes in the level of RI alpha and C alpha protein seem t o be due to a post-transcriptional event. The RII beta-overexpressing cell line, SK-RII beta, exhibited retarded monolayer growth, decreased DNA synthesis, inability to grow in soft agar, and reduced viability in serum-free or low-serum condition as compared to parental cell, SK- N-SH. These characteristics of SK-RII beta disappeared when the RII be ta expression was not fully induced. These results showed that the ele vation of RII beta and/or the decrease of RI alpha is closely related to the suppression of cell proliferation and the status of transformat ion of SK-N-SH neuroblastoma cell line.