Regulation of Cell Growth by Cyclic Adenosine 3′,5′-Monophosphate

Abstract

Abstract Growth stops at confluency in mouse 3T3 cells and in MA308 human diploid fibroblasts even with frequent changes of media. Accompanying this cessation of growth is an increase in the endogenous levels of cyclic adenosine 3',5' monophosphate (cyclic AMP). In WI38 human diploid fibroblasts cyclic AMP levels do not rise as the cells grow to high densities with frequent media renewals: however, if the medium is not replenished, cyclic AMP levels rise as growth slows, presumably due to depletion of some serum factor. Initiation of DNA synthesis in confluent 3T3 cells by the addition of fresh serum is preceded by a decrease in cyclic AMP levels. The cyclic AMP levels also decrease following addition of trypsin or insulin, agents which stimulate DNA synthesis and cell growth. Prostaglandin E1 (PGE1) which inhibits cell growth in L-929 cells, raises cyclic AMP levels. Insulin alone has no effect, but when added with PGE1 it will partially prevent the elevation of cyclic AMP levels and corresponding inhibition of growth. The results give further support for the proposal that cyclic AMP regulates cell growth and mediates contact inhibition of growth.