Sprouty1 haploinsufficiency accelerates pheochromocytoma development in Pten+/- mice

Abstract

Pheochromocytomas (PCCs) are rare catecholamine-secreting tumors arising from the chromaffin cells in the adrenal medulla. Closely related paragangliomas share developmental origin but arise extra-adrenally, in the paraganglia that belongs to the sympathetic and parasympathetic ganglia. Most PCCs are sporadic but around 25%-30% of them are associated with familial syndromes caused by germline mutations of at least ten genes (Gimenez-Roqueplo et al. 2012). The low incidence of pheochromocytomas poses difficulties to the development of diagnostic or prognostic markers as well as effective therapies and thus the development of novel animal and cellular models for the study of the disease is needed. Sprouty family of genes is composed of four members of feedback inhibitors of receptor tyrosine kinase signaling, that specifically target the MAPK pathway. As such, they have been proposed as tumor suppressors in several cancerous pathologies such as tumors of the prostate, thyroid or liver (Masoumi-Moghaddam et al. 2014). Here we present a novel mouse model of pheochromocytoma consisting of double heterozygous mice for Pten and Spry1. These animals develop pheochromocytomas that appear at earlier onset and grow at higher rate than those from Pten+/- mice

This work was supported by grants from Ministerio de Economía y Competitividad (BFU2010-17628 and BFU2013-47175) to ME and funding from Suport als Grups de Recerca (2014 SGR 138) from Generalitat de Catalunya to ME and XM-G. MV is supported by a predoctoral fellowship from AGAUR (Generalitat de Catalunya). AM was supported by predoctoral fellowships from Universitat de Lleida and Fundació Alícia Cuello de Merigó. CA is supported by a predoctoral fellowship from Universitat de Lleida.