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Article Dans Une Revue Journal of Clinical Endocrinology and Metabolism Année : 2009

Inhibition of adrenocortical carcinoma cell proliferation by steroidogenic factor-1 inverse agonists.

Résumé

CONTEXT: 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). MAIN OUTCOME MEASURES: 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. CONCLUSION: SF-1 inhibitors may represent a useful tool in the chemotherapy of ACTs.

Dates et versions

hal-00417317 , version 1 (15-09-2009)

Identifiants

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Mabrouka Doghman, Julie Cazareth, Dominique Douguet, Franck Madoux, Peter Hodder, et al.. Inhibition of adrenocortical carcinoma cell proliferation by steroidogenic factor-1 inverse agonists.. Journal of Clinical Endocrinology and Metabolism, 2009, 94 (6), pp.2178-83. ⟨10.1210/jc.2008-2163⟩. ⟨hal-00417317⟩
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