Cyclic AMP and the Transformation of Fibroblasts

Abstract

Cyclic AMP is found in a wide variety of organisms and cells. It is a chemical switch that regulates the activity of existing enzymes and also can induce the synthesis of new proteins. This chapter reviews the role of cyclic AMP in fibroblasts, especially the role of cyclic AMP in the transformation of these cells. The transformed fibroblasts grow faster than normal cells and have a greatly increased saturation density. The transformed cells look different, generally they are less spindly and more refractile in appearance; they are less adhesive to the substratum on which they are growing and will grow in soft agar, whereas normal cells will not; they have altered surface molecules and are readily agglutinated by plant lectins; they often secrete abnormal amounts of macromolecules; and have abnormal tRNA and increased aerobic glycolysis. Cyclic AMP has an important role in regulating many properties of normal fibroblasts. It is involved in controlling cell shape, adhesiveness to the substratum, motility, growth, agglutinability by lectins, and the synthesis of certain macromolecules. As a result of the transformation by chemical carcinogens, X-rays, oncogenic viruses, or spontaneous selection, cyclic AMP levels are decreased and this decrease produces some of the abnormal properties of transformed cells. Transformation by different viruses decreases adenylate cyclase activity by diverse mechanisms because a variety of transformation factors exist.