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. Copyright

dx.doi.org/10.1210/en.2014-1088, hdl.handle.net/1765/59228
Endocrinology
This work was funded by the European Commission 7th Framework Programme; grant id fp7/259735 - European Network for the Study of Adrenal Tumours - Structuring clinical research on adrenal cancers in adults (ENS@T-CANCER)
Department of Pathology

de Late, P.L, El Wakil, A, Jarjat, M, de Krijger, R.R, Heckert, L.L, Naquet, P, & Lalli, E. (2014). Vanin-1 inactivation antagonizes the development of adrenocortical neoplasia in Sf-1 transgenic mice. Endocrinology, 155(7), 2349–2354. doi:10.1210/en.2014-1088