Inhibitory effects of toremifene on N-methyl-N-nitrosourea and estradiol-17μ-induced endometrial carcinogenesis in mice

Abstract

Short- and long-term experiments were designed to determine the effects of toremifene (TOR) on estrogen-related endometrial carcinogenesis in mice. In the short-term experiment, a single low dose of TOR (0.2 mg/30 g body weight) decreased expression of c-fos, interleukin (IL)-1α, estrogen receptor (ER)-α mRNAs and corresponding proteins induced by estradiol-17β (E2), in the uteri of the ovariectomized mice. Expression of ER-β mRNA was increased by the TOR treatment, compared with the control. In the long-term experiment, 106 female ICR mice were given N-methyl-N-nitrosourea (MNU) into their uterine corpora. The animals were divided into four groups as follows: group 1, E2 diet (5 ppm) plus TOR (0.2 mg/30 g body weight, subcutaneously, every four weeks); group 2, E2 diet alone; group 3, basal diet plus TOR. Group 4 served as the control. TOR treatment decreased the incidence of MNU and E2-induced endometrial adenocarcinoma and atypical hyperplasia at the termination of the experiment (30 weeks after the start). These results suggest that TOR exerts preventive effects against estrogen-related endometrial carcinogenesis in mice, through the suppression of c-fos as well as IL-1α expression induced by E2. Such suppressive effects of TOR may be related to the decreased ER-α and increased ER-β expressions.