Pheochromocytomas in Nf1 knockout mice express a neural progenitor gene expression profile.

摘要: Pheochromocytomas are adrenal medullary tumors that typically occur in adult patients, with increased frequency multiple endocrine neoplasia type 2, von Hippel-Lindau disease, familial paraganglioma syndromes and neurofibromatosis 1 (NF1). arise mice a heterozygous knockout mutation of exon 31 the murine Nf1 gene, providing mouse model for pheochromocytoma development NF1. We performed microarray-based gene expression profiling study comparing tissue to normal medulla develop basis studying pathobiology these tumors. The findings demonstrate pheochromocytomas from express developmentally regulated genes involved early both CNS peripheral nervous system. One most highly overexpressed is receptor tyrosine kinase Ret, which known be transiently expressed developing gland, down-regulated adrenals often human pheochromocytomas. Real-time polymerase chain reaction validated microarray results immunoblots confirmed overexpression Ret protein. Other include Sox9, neural crest determinant, Hey 1, helps maintain progenitor status precursors. consistent recently proposed concept persistent progenitors might give rise suggest events predisposing tumor before formation or migration cells crest. However, competing possibility secondarily neoplastic transformation cannot ruled out. In either case, unique profile opens new applications pertinent stem suggests potential targets treatment eradication their