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

Perle Latre De Late, Abeer El Wakil, Marielle Jarjat, Ronald R. De Krijger, Leslie L. Heckert, Philippe Naquet, Enzo Lalli

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

18 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)2349-2354
Aantal pagina's6
TijdschriftEndocrinology
Volume155
Nummer van het tijdschrift7
DOI's
StatusGepubliceerd - jul. 2014
Extern gepubliceerdJa

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