title: Mifepristone inhibits extracellular matrix formation in uterine leiomyoma.
abstract: OBJECTIVE
  To characterize the efficacy of mifepristone treatment on extracellular matrix (ECM) production in leiomyomas.
  
  
  METHODS
  Laboratory study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  None.
  
  
  METHODS
  Treatment of human immortalized two-dimensional (2D) and three-dimensional (3D) leiomyoma and myometrial cells with mifepristone and the progestin promegestone (R5020).
  
  
  METHODS
  Expression of COL1A1, fibronectin, versican variant V0, and dermatopontin in treated leiomyoma cells by Western blot analysis and confirmatory immunohistochemistry staining of treated 3D cultures.
  
  
  RESULTS
  Treatment with progestin stimulated production of COL1A1, fibronectin, versican, and dermatopontin. Mifepristone treatment inhibited protein production of these genes, most notably with versican expression. Combination treatment with both the agonist and antagonist further inhibited protein expression of these genes. Immunohistochemistry performed on 3D cultures demonstrated generalized inhibition of ECM protein concentration.
  
  
  CONCLUSIONS
  Our study demonstrated that the progesterone agonist R5020 directly stimulated extracellular matrix components COL1A1, fibronectin, versican, and dermatopontin production in human leiomyoma cells. Progesterone antagonist mifepristone decreased protein production of these genes to levels comparable with untreated leiomyoma cells.
authors.affiliation: Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Amrita
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Minnie
authors.initials: M
authors.lastname: Malik
authors.affiliation: Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Joy
authors.initials: J
authors.lastname: Britten
authors.affiliation: Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jeris
authors.initials: J
authors.lastname: Cox
authors.affiliation: Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Electronic address: william.catherino@usuhs.edu.
authors.forename: William H
authors.initials: WH
authors.lastname: Catherino
mesh_terms: D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015735:Mifepristone / Q000494:pharmacology*; D011397:Promegestone / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D006727:Hormone Antagonists; D015735:Mifepristone; D011397:Promegestone
keywords: Collagen 1A1; dermatopontin; extracellular matrix; fibronectin; mifepristone; progesterone agonist; versican