Inhibition of adrenocortical carcinoma cell proliferation by steroidogenic factor-1 inverse agonists.
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.
Doghman
Mabrouka
M
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
Cazareth
Julie
J
Douguet
Dominique
D
Madoux
Franck
F
Hodder
Peter
P
Lalli
Enzo
E