A novel cannabinoid reduces uterine hyperplasia caused by tamoxifen in mice
Uterine hyperplasia is characterized by overgrowth of cells in the lining of the uterus, causing it to become thicker than usual. Uterine hyperplasia can lead to irregular or heavy menstrual bleeding, and in more severe cases, it can increase the risk of developing endometrial cancer. The hormone estrogen plays a central role in endometrial proliferation, by binding to the estrogen receptor (ER) in the epithelial endometrium. Many ER-positive breast cancer patients develop uterine hyperplasia, and it was found that some Selective Estrogen Receptor Modulators (SERMs) such as tamoxifen act as antagonists in the breast and as agonists in the uterus. In the breast, tamoxifen blocks estrogen from binding the ER and hinders cell proliferation, while in the uterus tamoxifen binds the ER and coactivators complex and induces cell proliferation. In the Meiri’s lab we have found a novel cannabinoid that reduces the expression of the ER through the Hippo signaling pathway, and enhances the effect of tamoxifen on breast cancer. Therefore, we hypothesized this cannabinoid may reduce ER expression in the endometrium, and thus attenuate tamoxifen-induced uterine hyperplasia. We utilized a new model to study tamoxifen-induced hyperplasia, and found the cannabinoid treatment decreased uterine mass, luminal thickness and proliferation of epithelial cells, resulting also in less tissue dysmorphology. To conclude, this novel cannabinoid can relieve uterine hyperplasia manifestations, and could be combined with tamoxifen for ER-positive breast cancer patients. By treating endometrial hyperplasia patients may avoid surgery and preserve fertility, have increased long-term health and quality of life and adhere to SERMs treatment.
