Cyclic adenosine 3':5'-monophosphate and protein kinase activity in insulin-dependent and -independent mammary tumors.
Approximately 70% of primary 7,12-dimethylbenz(alpha)-anthracene-induced mammary tumors regressed when (tumor-bearing) rats were made diabetic after treatment with streptozotocin. In the intact animal, cyclic adenosine 3':5"-monophosphate (cAMP) levels of tumors that regressed following the induction of diabetes were initially 4-fold lower than in unresponsive tumors but increased 4-fold during regression. The insulin-independent tumors showed no statistically significant changes. cAMP binding in cytosol of regressing tumors was about 80% above the initial values at 36 hr after therapy but decreased to about 45% 1 week later. On the contrary, the binding capacity of the nuclei showed a 56% increase at 36 hr and increased gradually to about 3-fold 1 week later. Within 36 hr after treatment, total histone kinase activity increased 127% in the cytosol and 153% in the nuclei of regressing tumors. The increment of histone kinase activity was almost totally in the cAMP-dependent component of the enzyme. These changes were not apparent in insulin-independent tumors. The results are interpreted to indicate that mammary tumor regression due to diabetes involves the cAMP system and occurs through a sequence of events similar to those observed during regression induced by either ovariectomy or dibutyryl cAMP (cyclic adenosine 3':5'-monophosphate) treatment.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D005260:Female; D007328:Insulin; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D006656:Protamine Kinase / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D013311:Streptozocin; D013997:Time Factors
D007328:Insulin; D013311:Streptozocin; D000242:Cyclic AMP; D011494:Protein Kinases; D006656:Protamine Kinase