Cyclic AMP-mediated transformation of rat cells transformed by temperature-sensitive mouse sarcoma virus

Abstract

SEVERAL lines of evidence suggest that adenosine 3′,5′-cyclic monophosphate (cyclic AMP) is involved in the regulation of growth and other properties of cultured cells (for review, see ref. 1). Specifically, various reports have shown a correlation between the abnormal growth and morphological properties of virus-transformed cells and low levels of cyclic AMP2,3. Treatment of these transformed cells with cyclic AMP, cyclic AMP analogues, or agents that raise cyclic AMP levels restores growth and morphological properties characteristic of normal cells4–7. The use of cells transformed by temperature-sensitive (ts) mutants of Rous sarcoma virus (RSV) or mouse sarcoma virus (MSV)8,9 as well as ts host cell mutants10,11 strengthened the evidence relating viral transformation and cyclic AMP levels. Other evidence obtained in similar virally transformed cell systems, however, has failed to confirm the inverse relationship between cyclic AMP levels and cell growth rate and transformation by RNA and DNA tumour viruses12–15. We now report that the exogenous addition of cyclic AMP mediates the morphological transformation of rat cells transformed by a ts mutant of MSV at the non-permissive temperature. Correspondingly, expression of the transformed phenotype by cells grown at the permissive temperature is associated with increased levels of endogenous cyclic AMP.