Anticarcinogenic effect of retinoids on 7,12-dimethylbenz(a)anthracene-induced mammary tumor induction, and its relationship to cyclic AMP-dependent protein kinase

Abstract

Administration of 13-cis retinoic acid and N-(4-hydroxyphenyl) retinamide daily in the diet to female Sprague-Dawley rats beginning one day after intubation with 7,12-dimethylbenz(a)anthracene (DMBA) prolonged the latency periods and inhibited the percentage incidence of mammary tumors. A significant reduction in the total number of tumors was also evident. The inhibition of mammary tumor growth by retinoids was associated with a significant increase (3-fold) in cytosolic cAMP-binding and histone kinase activities. The increase of histone kinase activity was almost totally in the cAMP-dependent protein kinase Type II. Retinoic acid increased the amount of the regulatory subunit (R 11) rather than altering its cAMP binding affinity. These results suggest that cAMP-dependent protein kinase Type II may be involved in mediating the retinoid action in the inhibition of mammary tumor growth in , vivo .