| Abstract: | It has been shown that a marked increase in the levels of Rlα sub-units and a decrease in RIIβ sub-unit levels correlate with neoplastic transformation or with the mitogenic response of normal cells to hormones and growth factors. The selective down-regulation of RIα and the following induction of RIIβ determine cell-growth arrest and differentiation of several cancer cells. To directly address the question whether the 2 protein-kinase-A(PKA) isoforms play different roles in the control of proliferation and cell-cycle distribution, we introduced and over-expressed the different PKA sub-units in Chinese-hamster-ovary (CHO) cells via retroviral-vector-mediated gene transfer. Whereas CHO cells treated with RIα anti-sense oligodeoxynucleotides were growth arrested and accumulated in the G0/G1 phases of the cell cycle, infection of CHO cells with a retroviral vector in order to over-express RIα determined growth advantages in monolayer conditions and substantially increased their cloning efficiency in soft agar. These events correlated with a sustained percentage of cells in S phase induced by RIα over-expression in the infected cells. In contrast, CHO cells infected with retroviral vectors over-expressing either a RIIβ sub-unit or a Cα catalytic sub-unit of PKA exhibited growth arrest within a few days of culture and accumulated in the G2-M phase of the cell cycle. The results of our study demonstrate that the different PKA sub-units play different and specific roles in the control of cell growth and cell-cycle distribution. |
