Expression of retinoic acid receptors in human endometrial carcinoma

The retinoids (vitamin A and its biologically active derivatives) are essential for the health and survival of the individual. Several studies have reported a strong rationale for the use of retinoids in cancer treatment and chemoprevention. It has been discovered that expression of retinoic acid receptor (RAR) β is frequently silenced in epithelial carcinogenesis, which has led to the hypothesis that RARβ could act as a tumor suppressor. However, the status of RARβ in human endometrial carcinoma has not been examined. In the present study, we initially studied the effects of retinoic acid on cell proliferation and the expression of RARα, RARβ, and RARγ using AM580 (a RAR-specific agonist) in the Ishikawa endometrial cancer cell line. We also examined the expression of RAR in human eutopic endometrium (30 cases), endometrial hyperplasia (28 cases), and endometrial carcinoma (103 cases) using immunohistochemistry. Finally, we correlated these findings with the clinicopathological parameters. In vitro, cell growth was inhibited and RARβ and RARγ mRNA was significantly induced by AM580, compared with vehicle controls, whereas RARα mRNA was significantly attenuated by AM580, compared with vehicle. RARβ was detected predominantly in endometrial hyperplasia, compared with endometrial carcinoma. No statistically significant correlation was obtained between the expression of any other RAR subtypes and clinicopathological parameters in human endometrial carcinoma. The results of our study demonstrate that AM580 inhibits cell growth and induces RARβ mRNA expression in the Ishikawa cell line, and the expression level of RARβ in endometrial carcinoma is significantly lower than that in endometrial hyperplasia. AM580 might therefore be considered as a potential treatment for endometrial carcinoma. (Cancer Sci 2008; 99: 267–271)