REGRESSION OF HORMONE-DEPENDENT MAMMARY-TUMORS IN SPRAGUE-DAWLEY RATS AS A RESULT OF TAMOXIFEN OR PHARMACOLOGIC DOSES OF 17-BETA-ESTRADIOL - CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE-MEDIATED EVENTS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 66  (2) , 321-326
Abstract
The estrogen and cAMP-binding activities changed markedly when 7,12-dimethylbenz[a]anthracene-induced mammary tumor cells of Sprague-Dawley rats regressed following daily injections of tamoxifen or pharmacologic doses of 17.beta.-estradiol. cAMP binding increased 8- to 10-fold; estrogen binding increased 2- to 3-fold in regressing tumor nuclei at 5 days after either treatment, causing an inversion of the ratio of estrogen binding to cAMP binding found in growing tumor nuclei. Concomitantly, both binding activities were depleted from the cytosol. In the regressing tumors, the cAMP level increased 2-fold and nuclear cAMP-dependent protein kinase activity increased 3- to 4-fold, with a 70-80% decrease in the cytoplasmic protein kinase activity. The rise in the nuclear protein kinase activity was abolished when cycloheximide was given with tamoxifen or with high doses of 17.beta.-estradiol; the increased acetivity may be due to new protein synthesis. In the regressing tumor nuclei, the phosphorylation of the regression-associated proteins increased; the phosphorylation of growth-associated proteins decreased. The mammary tumor regression induced by tamoxifen or high doses of estrogen probably proceed through a series of cAMP-mediated events.