The role of cAMP in regulating tumour cell growth

Addition of cAMP to various cultured cell types has a dramatic effect on cell growth. Both positive and negative effects on growth have been demonstrated. Analysis of mutants with altered cAMP dependent protein kinases suggests that tumour cells do not require a functional endogenous cAMP system for normal cell cycling. Whether or not cAMP stimulates or inhibits cell growth depends on the cell type, the oncogene driving its growth, the dose of cAMP and the environment of the cell. The ras gene product does not appear to be a component of the adenylate cyclase system, and no other oncogenes have been shown to use cAMP as a second messenger. However, another class of oncogenes possesses a serine/threonine kinase activity analogous to that of cAMP dependent protein kinase. Several oncogene products and growth factor receptors are phosphorylated on serine residues, suggesting that some oncogene products, such as pp60src may be targets for the action of cAMP. The role of cAMP in tumour cell growth may be to modulate the activity of the oncogenes or their protein targets which control cell growth.