title: Ovarian steroid hormones modulate the expression of progesterone receptors and histone acetylation patterns in uterine leiomyoma cells.
abstract: Uterine leiomyomas are the most common benign smooth muscle cell tumors in women. Estrogen (E2), progesterone (P4) and environmental factors play important roles in the development of these tumors. New treatments, such as mifepristone, have been proposed. We evaluated the gene expression of total (PRT) and B (PRB) progesterone receptors, and the histone acetyltransferase (HAT) and deacetylase (HDAC) activity after treatment with E2, P4 and mifepristone (RU486) in primary cell cultures from uterine leiomyoma and normal myometrium. Compared to myometrium, uterine leiomyoma cells showed an increase in PRT mRNA expression when treated with E2, and increase in PRB mRNA expression when treated with E2 and P4. Treatment with mifepristone had no significant impact on mRNA expression in these cells. The HDAC activity was higher in uterine leiomyoma compared to myometrial cells after treatment with E2 and E2 + P4 + mifepristone. HAT activity was barely detectable. Our results suggest that ovarian steroid hormones modulate PR, and mifepristone was unable to decrease PRT and PRB mRNA. The higher activity of HDAC leiomyoma cells could be involved in transcriptional repression of genes implicated in normal myometrium cell function, contributing to the maintenance and growth of uterine leiomyoma.
authors.affiliation: a Programa de Pós-Graduação em Medicina: Ciências Médicas, Faculdade de Medicina da Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|b Laboratório de biologia molecular endócrino e tumoral , Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|c Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Gabriela Dos Santos
authors.initials: GDS
authors.lastname: Sant'Anna
authors.affiliation: b Laboratório de biologia molecular endócrino e tumoral , Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|c Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Ilma Simoni
authors.initials: IS
authors.lastname: Brum
authors.affiliation: b Laboratório de biologia molecular endócrino e tumoral , Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|c Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.|d Programa de Pós-Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre , Porto Alegre , Brazil , and.
authors.forename: Gisele
authors.initials: G
authors.lastname: Branchini
authors.affiliation: b Laboratório de biologia molecular endócrino e tumoral , Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|c Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.
authors.forename: Lolita Schneider
authors.initials: LS
authors.lastname: Pizzolato
authors.affiliation: b Laboratório de biologia molecular endócrino e tumoral , Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|c Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.|e Departamento de Ginecologia e Obstetrícia , Faculdade de Medicina da UFRGS , Porto Alegre , Brazil.
authors.forename: Edison
authors.initials: E
authors.lastname: Capp
authors.affiliation: a Programa de Pós-Graduação em Medicina: Ciências Médicas, Faculdade de Medicina da Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|b Laboratório de biologia molecular endócrino e tumoral , Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul , Porto Alegre , Brazil.|c Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.|e Departamento de Ginecologia e Obstetrícia , Faculdade de Medicina da UFRGS , Porto Alegre , Brazil.
authors.forename: Helena von Eye
authors.initials: HVE
authors.lastname: Corleta
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007889:Leiomyoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology; D009215:Myometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D011372:Progestins / Q000378:metabolism / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
chemical_list: D004967:Estrogens; D006727:Hormone Antagonists; D009363:Neoplasm Proteins; D011372:Progestins; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases
keywords: Estradiol; histone deacetylase activity; mifepristone; progesterone; uterine leiomyoma