Estradiol Dependency of Tumor Growth, Levels of Steroid Receptor Contents and Enzymic Activities in Rat Breast Cancer Tissues

Abstract

To study the nature of tumor growth and regression, the mammary cancer model in Sprague-Dawley rats, induced by N-nitrosomethylurea(NMU) was analyzed with a view of biochemical response to physiological modification of host estradiol system, such as ovariectomy, tamoxifen treatment or estradiol reinjection. The growth and regression of the tumors were monitored by the tumor size variation in response to the treatment. The surgical removal of estradiol generation system such as ovariectomy and the medical treatment of estradiol antagonist, tamoxifen, markedly decreased the tumor size within two weeks, while the replenishment of estradiol by intraperitoneal reinjection stimulated the tumor growth. With these changes of tumor size, the efficiency of the functional hormonal apparatus was checked by determination of the contents of the estradiol and progesterone receptor in the cytosol and nuclear fractions, respectively. The receptor analysis showed that the contents of the cytoplasmic estradiol and progesterone receptor varied directly in response to estradiol state of the host namely, decreased level at reduced tumor volume and increased level at tumor-stimulated state. The changing patterns of the contents of the nuclear estradiol and progesterone receptors were similar to those of the cytoplasmic ones. In relation with the changes of receptor contents, the radical-related enzymes were monitored for their activities such as peroxidase, catalase, superoxide dismutase and glutathione transferase. Among them only the peroxidase activities showed the positive correlation with the estradiol receptor contents. These results indicated that the growth and regression of the mammary tumors could be deeply related with the receptor status of estradiol system and the activities of peroxidase.