INVERSE RELATION BETWEEN ESTROGEN RECEPTORS AND CYCLIC ADENOSINE 3'-5'-MONOPHOSPHATE-BINDING PROTEINS IN HORMONE-DEPENDENT MAMMARY-TUMOR REGRESSION DUE TO DIBUTYRYL CYCLIC ADENOSINE 3'-5'-MONOPHOSPHATE TREATMENT OR OVARIECTOMY

Abstract

During the growth arrest of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas following ovariectomy or N6,O2''-dibutyryl cyclic AMP (DBcAMP) treatment, a change in the specific estrogen and cAMP binding to tumor proteins was observed. Three days after ovariectomy or DBcAMP treatment of the hosts, cAMP binding increased 5- and 2-fold in the nuclei and cytosol of tumors, respectively, whereas nuclear and cytoplasmic estrogen binding decreased by 70 and 25%, respectively. These changes in cAMP- and estrogen-binding activities were detectable within 1 day after ovariectomy or DBcAMP treatment, and the changes were reversed when resumption of tumor growth was induced by the injection of estradiol valerate or cessation of DBcAMP treatment. When 7,12-dimethylbenz(a)anthracene-induced tumors failed to regress after ovariectomy or DBcAMP treatment, the change in estrogen and cAMP binding did not occur. Concomitant with the increase of cAMP-binding activity in regressing tumors were increases in histone kinase activity and the cAMP content of the tumors. These increases in cAMP-binding and protein kinase activities were blocked by cycloheximide. An interaction may occur between a steroid hormone and cAMP in the growth control of a hormone-dependent mammary tumor.