Anticarcinogenic effect of retinoids on 7,12-dimethylbenz(a)anthracene-induced mammary tumor induction, and its relationship to cyclic AMP-dependent protein kinase.
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 (R11) 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.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D006656:Protamine Kinase / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D012176:Retinoids / Q000494:pharmacology*
D012176:Retinoids; D015127:9,10-Dimethyl-1,2-benzanthracene; D000242:Cyclic AMP; D011494:Protein Kinases; D006656:Protamine Kinase