Steroid Hormone Intervenes in the Endometrial Tumorigenesis of Pten Ablation

BACKGROUND Endometrial cancer, the most common gynecological cancer, is closely associated with endometrial hyperplasia, unopposed estrogen exposure, and genetic alterations. Phosphatase and tensin homologue (PTEN) is a tumor suppressor genes completely lost or mutated in >50% of primary endometrioid endometrial cancers. Estrogen-dependent endometrioid carcinoma is the most common type of endometrial cancer. Progesterone is a hormone that antagonizes the growth-promoting properties of estrogen in the uterus. Progestin is used as a conservative endocrine treatment of early endometrial cancer in order to preserve fertility as well as a palliative measure for advanced-stage patients. Progesterone therapy has been shown to be effective in preventing endometrial cancer as well as controlling growth of the endometrium. However, the effectiveness of progestin for women with endometrial cancer is less clear. METHODS In order to understand the effect of steroid hormone on endometrial cancer progression, we used a mouse endometrial cancer model with conditional loss of Pten in the mouse uterus (PR (cre/+) Pten (f/f) , Pten(d/d) ). To assess the effect of steroid hormones, ovariectomized Pten(f/f) and Pten(d/d) mice were treated with estrogen or progesterone over a period of three month. RESULTS Uterine weight gain was significantly decreased in ovariectomized PR (cre/+) Pten(f/f) mice compared to intact PR (cre/+) Pten(f/f) mice. Ovariectomized PR (cre/+) Pten(f/f) mice treated with P4 or vehicle also exhibited decreased uterine cancer size compared with intact PR (cre/+) Pten(f/f) mice. Proliferation of ovariectomized PR (cre/+) Pten(f/f) mice treated with P4 is highly decreased compared to other groups. The levels of stromal progesterone receptor were highly increased in ovariectomized PR (cre/+) Pten(f/f) mice treated with P4 which resulted in decreased epithelial proliferation. CONCLUSIONS These results suggest that P4 treatment significantly reduces tumor mass but does not affect cancer progression in PR (cre/+) Pten(f/f) mice.