CYCLIC ADENOSINE 3'-5'-MONOPHOSPHATE AND PROTEIN-KINASE ACTIVITY IN INSULIN-DEPENDENT AND INSULIN-INDEPENDENT MAMMARY-TUMORS

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (7) , 2501-2504
Abstract
Approximately 70% of primary 7,12-dimethylbenz(a)anthracene-induced mammary tumors regressed when (tumor-bearing) rats were made diabetic after treatment with streptozotocin. In the intact animal, cyclic[c]AMP 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 h after therapy but decreased to about 45% 1 wk later. On the contrary, the binding capacity of the nuclei showed a 56% increase at 36 h and increased gradually to about 3-fold 1 wk later. Within 36 h 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. Mammary tumor regression due to diabetes may involve the cAMP system and occurs through a sequence of events similar to those observed during regression induced by either ovariectomy or dibutyryl cAMP treatment.