title: Decorin induced by progesterone plays a crucial role in suppressing endometriosis.
abstract: Dienogest, a synthetic progestin, has been shown to be effective against endometriosis, although it is still unclear as to how it affects the ectopic endometrial cells. Decorin has been shown to be a powerful endogenous tumor repressor acting in a paracrine fashion to limit tumor growth. Our objectives were to examine the direct effects of progesterone and dienogest on the in vitro proliferation of the human ectopic endometrial epithelial and stromal cell lines, and evaluate as to how decorin contributes to this effect. We also examined DCN mRNA expression in 50 endometriosis patients. The growth of both cell lines was inhibited in a dose-dependent manner by both decorin and dienogest. Using a chromatin immunoprecipitation assay, it was noted that progesterone and dienogest directly induced the binding of the decorin promoter in the EMOsis cc/TERT cells (immortalized human ovarian epithelial cells) and CRL-4003 cells (immortalized human endometrial stromal cells). Progesterone and dienogest also led to significant induced cell cycle arrest via decorin by promoting production of p21 in both cell lines in a dose-dependent manner. Decorin also suppressed the expression of MET in both cell lines. We confirmed that DCN mRNA expression in patients treated with dienogest was higher than that in the control group. In conclusion, decorin induced by dienogest appears to play a crucial role in suppressing endometriosis by exerting anti-proliferative effects and inducing cell cycle arrest via the production of p21 human ectopic endometrial cells and eutopic endometrial stromal cells.
authors.affiliation: Department of Obstetrics and GynecologyOsaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, JapanDepartment of Obstetrics and GynecologyGraduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Yoshihiro Joshua
authors.initials: YJ
authors.lastname: Ono
authors.affiliation: Department of Obstetrics and GynecologyOsaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, JapanDepartment of Obstetrics and GynecologyGraduate School of Medical Science, Kanazawa University, Kanazawa, Japan y-terai@poh.osaka-med.ac.jp.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Terai
authors.affiliation: Department of Obstetrics and GynecologyOsaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, JapanDepartment of Obstetrics and GynecologyGraduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanabe
authors.affiliation: Department of Obstetrics and GynecologyOsaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, JapanDepartment of Obstetrics and GynecologyGraduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hayashi
authors.affiliation: Department of Obstetrics and GynecologyOsaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, JapanDepartment of Obstetrics and GynecologyGraduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Obstetrics and GynecologyOsaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, JapanDepartment of Obstetrics and GynecologyGraduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of Obstetrics and GynecologyOsaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, JapanDepartment of Obstetrics and GynecologyGraduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kyo
authors.affiliation: Department of Obstetrics and GynecologyOsaka Medical College, 2-7, Daigaku-machi, Takatsuki, Osaka 569-8686, JapanDepartment of Obstetrics and GynecologyGraduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Ohmichi
mesh_terms: D000328:Adult; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D058575:Decorin / Q000235:genetics / Q000502:physiology*; D004715:Endometriosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D010049:Ovarian Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology* / Q000627:therapeutic use; D012189:Retrospective Studies; D015533:Transcriptional Activation / Q000187:drug effects; D055815:Young Adult
chemical_list: C546878:DCN protein, human; D058575:Decorin; C023635:dienogest; D011374:Progesterone; D009277:Nandrolone
keywords: cell cycle arrest; decorin; dienogest; endometriosis; p21; progesterone