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Endocrinology. 2014 Jul;155(7):2349-54. doi: 10.1210/en.2014-1088. Epub 2014 Apr 8.

Vanin-1 inactivation antagonizes the development of adrenocortical neoplasia in Sf-1 transgenic mice.

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Institut de Pharmacologie Moléculaire et Cellulaire CNRS (P.L.D.L., A.E.W., M.J., E.L.) Valbonne 06560, France; Associated International Laboratory for the Study of the ALterations of Gene Expression in Childhood Cancers CNRS (P.L.D.L., A.E.W., M.J., E.L.), Valbonne 06560, France; Université de Nice-Sophia Antipolis (P.L.D.L., A.E.W., M.J., E.L.), Valbonne 06560, France; Department of Pathology (R.R.K.), Erasmus MC-University Medical Center, Rotterdam 3015, The Netherlands; Department of Molecular and Integrative Physiology (L.L.H.), University of Kansas Medical Center, Kansas City, Kansas 66160; Centre d'Immunologie de Marseille-Luminy (P.N.), Aix-Marseille University, UM2, Marseille, France; Institut National de la Santé et de la Recherche Médicale (P.N.), U1104, Marseille, France; and Centre National de la Recherche Scientifique (P.N.), UMR7280, Marseille, France.


SF-1 (NR5A1) overexpression can induce adrenocortical tumor formation in transgenic mice and is associated with more severe prognosis in patients with adrenocortical cancer. In this study we have identified Vanin-1 (Vnn1), a SF-1 target gene, as a novel modulator of the tumorigenic effect of Sf-1 overexpression in the adrenal cortex. Vanin-1 is endowed with pantetheinase activity, releasing cysteamine in tissues and regulating cell response to oxidative stress by modulating the production of glutathione. Sf-1 transgenic mice developed adrenocortical neoplastic lesions (both dysplastic and nodular) with a frequency increasing with age. Genetic ablation of the Vnn1 gene in Sf-1 transgenic mice significantly reduced the severity of neoplastic lesions in the adrenal cortex. This effect could be reversed by treatment of Sf-1 transgenic/Vnn1 null mice with cysteamine. These data show that alteration of the mechanisms controlling intracellular redox and detoxification mechanisms is relevant to the pathogenesis of adrenocortical neoplasia induced by SF-1 overexpression.

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