Regression with secretory changes of ovary-independent rat mammary carcinoma by pharmacological doses of estrogen.

MT6 tumor is a transplantable ovary- and prolactin-independent rat mammary carcinoma containing estrogen and progesterone receptors. The effects of daily injections of 1 mg or 10 micrograms of 17 beta-estradiol for 28 days on the morphological changes and the proliferation and death of MT6 cells grown in male inbred Sprague-Dawley rats were investigated. Uptake values of 5-[125I]iodo-2'-deoxyuridine per g of living tumor, used as an index of cell proliferation, were not significantly reduced by treatment with 1 mg of 17 beta-estradiol. When tumor cell proliferation was evaluated by labeling with 5-[125I]iodo-2'-deoxyuridine just before the treatment, the radioactivity incorporated by the whole tumor remained almost unchanged in intact rats but was decreased slightly on day 21 and significantly on day 28 of the treatment in the rats treated with 1 mg of 17 beta-estradiol. Secretory changes characterized by the appearance of secretion in the lumina, vacuolation in the cytoplasm, marked increase in vesicular endoplasmic reticulum, accumulation of mature protein secretory granules and abundance of lipid droplets were observed in MT6 cells in rats treated with 1 mg of 17 beta-estradiol from the 14th day of treatment. On the 28th day, necrosis of MT6 cells with secretory changes was found. These changes were not found in intact rats or rats treated daily with 10 micrograms of 17 beta-estradiol. These findings suggest that the inhibitory effect of daily injections of 1 mg of 17 beta-estradiol on the growth of ovary- and prolactin-independent MT6 tumor is mainly due to secretory changes followed by loss of tumor cells induced by pharmacological doses of estrogens.