title: Inhibition of adrenocortical carcinoma cell proliferation by steroidogenic factor-1 inverse agonists.
abstract: BACKGROUND
  Transcription factor steroidogenic factor-1 (SF-1) plays a pivotal role in the control of adrenocortical cell steroidogenesis and proliferation. SF-1 amplification and overexpression are found in most cases of childhood adrenocortical tumors (ACTs).
  
  
  OBJECTIVE
  Our objective was to investigate the effect of SF-1 inverse agonists of the alkyloxyphenol and isoquinolinone classes on the proliferation of human adrenocortical cell lines expressing SF-1 (H295R), in conditions of basal and increased SF-1 expression, or negative for SF-1 expression (SW-13).
  
  
  METHODS
  Proliferation assays, immunoblots, flow cytometric analyses, steroid hormone assays, and reverse transcription quantitative PCR were used.
  
  
  RESULTS
  SF-1 inhibitors of the alkyloxyphenol class displayed a dose-dependent inhibitory effect on both SF-1-positive and -negative ACT cells, whereas SF-1 inverse agonists of the isoquinolinone class selectively inhibited cell proliferation elicited by SF-1 overexpression. These drugs also inhibited stimulated steroid hormone secretion and CYP21 and CYP17 mRNA expression.
  
  
  CONCLUSIONS
  SF-1 inhibitors may represent a useful tool in the chemotherapy of ACTs.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6097, Université de Nice-Sophia Antipolis, Valbonne 06560, France
authors.forename: Mabrouka
authors.initials: M
authors.lastname: Doghman
authors.forename: Julie
authors.initials: J
authors.lastname: Cazareth
authors.forename: Dominique
authors.initials: D
authors.lastname: Douguet
authors.forename: Franck
authors.initials: F
authors.lastname: Madoux
authors.forename: Peter
authors.initials: P
authors.lastname: Hodder
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli