Characterization and Estrogen Stimulation of Cytoplasmic Progesterone Receptor in the Ovarian-dependent MXT-3590 Mammary Tumor Line

The purpose of this study is to characterize the cytoplasmic progesterone receptor of the ovarian-dependent MXT mouse mammary tumor line and to demonstrate that the levels of this receptor are under positive control by estrogen. MXT-3590 is a transplantable mouse mammary tumor line originally induced by urethan treatment in C57BL x DBAf F 1 mice. The tumor is an ovarian-dependent well-differentiated ductal carcinoma which responds by rapid growth to estradiol benzoate and to medroxyprogesterone acetate (Depo Provera). These hormones given simultaneously result in a greater than additive growth effect. This synergism indicates that progesterone has no antagonistic effect on estrogen action as it does in many other model systems. Progesterone receptor was measured at 4° with [³H]progesterone in a brief exposure dextran-coated charcoal assay. The dissociation constant of the cytoplasmic receptor is approximately 5 nM, and the binding was specific for progesterone and its synthetic analog R5020. Specific progesterone binding appeared in both the 4S and 8S regions of 5 to 20% postlabeled sucrose density gradients. The quantity of progesterone receptor measured in MXT-3590 (28 fmol/ mg tissue) falls after ovariectomy (5 fmol/mg tissue) and increases (20 fmol/mg tissue) following a s.c. injection of 2.5 μg of estradiol-17β. Thus, MXT-3590 provides evidence in an experimental mammary carcinoma for the association between estrogen action and positive progesterone receptor control. By virtue of its readily measured and well-characterized estrogen and progesterone receptors, MXT-3590 provides a promising model system in which to study growth control by estrogen and progesterone in a neoplastic tissue.