title: Menstrual cyclic change of metastin/GPR54 in endometrium.
abstract: Metastin/kisspeptin is encoded by KISS1 and functions as an endogenous ligand of GPR54. Interaction of metastin with GPR54 suppresses metastasis and also regulates release of gonadotropin-releasing hormone, which promotes secretion of estradiol (E2) and progesterone (P4). We have previously demonstrated epigenetic regulation of GPR54 in endometrial cancer and the potent role of metastin peptides in inhibiting metastasis in endometrial cancer. However, little is known about how the metastin-GPR54 axis is regulated in the endometrium, the precursor tissue of endometrial cancer. Endometrial stromal cells (ESCs) and endometrial glandular cells (EGCs) within the endometrium show morphological changes when exposed to E2 and P4. In this study, we show that metastin expression is induced in ESCs through decidualization, but is repressed in glandular components of atypical endometrial hyperplasia (AEH) and endometrial cancer relative to EGCs. The promoter of GPR54 is unmethylated in normal endometrium and in AEH. These results indicate metastin may function in decidualized endometrium to prepare for adequate placentation but this autocrine secretion of metastin is deregulated during oncogenesis to enable tumor cells to spread.
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan, babatsu@kuhp.kyoto-u.ac.jp.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Baba
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Kang
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hosoe
authors.forename: Budiman
authors.initials: B
authors.lastname: Kharma
authors.forename: Kaoru
authors.initials: K
authors.lastname: Abiko
authors.forename: Noriomi
authors.initials: N
authors.lastname: Matsumura
authors.forename: Junzo
authors.initials: J
authors.lastname: Hamanishi
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Koshiyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Mandai
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D000328:Adult; D004714:Endometrial Hyperplasia / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism*; D008597:Menstrual Cycle / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011374:Progesterone / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D000074502:Receptors, Kisspeptin-1; D017154:Stromal Cells / Q000378:metabolism
chemical_list: C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D011374:Progesterone; D004958:Estradiol