MODULATION OF CELL-GROWTH, P34(CDC2) AND CYCLIN-A LEVELS BY SV40 LARGE T-ANTIGEN

Immortalization of rat lung epithelial cells by either wild-type SV-40 T antigen, a mutant form of T antigen that cannot bind pRb, or a temp erature-sensitive T antigen increased by five- to 20-fold the steady s tate levels of p34cdc2 and cyclin A, positive regulators of progressio n through the cell cycle. Increased abundance of p34cdc2 was not accom panied by equivalent increases in cdc2 mRNA, indicating that increased expression of p34cdc2 is due, at least partially, to post-transcripti onal mechanisms. Levels of p34cdc2 and cyclin A protein in cells immor talized with a temperature-sensitive T antigen remained elevated at th e restrictive temperature unless T antigen was reduced to levels signi ficantly below those where proliferation ceased, indicating that these two functions can be dissociated. These results show that SV-40 T ant igen can dramatically enhance the expression of certain cell cycle reg ulatory proteins by mechanisms that are independent of pRb binding and cell growth status.