title: Expression of retinoic acid receptors in human endometrial carcinoma.
abstract: 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) beta is frequently silenced in epithelial carcinogenesis, which has led to the hypothesis that RAR beta could act as a tumor suppressor. However, the status of RAR beta 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 RAR alpha, RAR beta, and RAR gamma 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 RAR beta and RAR gamma mRNA was significantly induced by AM580, compared with vehicle controls, whereas RAR alpha mRNA was significantly attenuated by AM580, compared with vehicle. RAR beta 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 RAR beta mRNA expression in the Ishikawa cell line, and the expression level of RAR beta in endometrial carcinoma is significantly lower than that in endometrial hyperplasia. AM580 might therefore be considered as a potential treatment for endometrial carcinoma.
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Tanabe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niikura
authors.forename: Tadao
authors.initials: T
authors.lastname: Takano
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagase
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ito
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hayashi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D004714:Endometrial Hyperplasia / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001565:Benzoates; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D013764:Tetrahydronaphthalenes; C082925:retinoic acid receptor beta; C068073:Am 580; D014212:Tretinoin