CITED1 expression in wilms’ tumor and embryonic kidney

Harold N. Lovvorn, III, Jenifer Westrup, Shaun Opperman, Scott C. Boyle, Genbin Shi, James Anderson, Elizabeth J. Perlman, Alan O. Perantoni, Marcia Wills and Mark de Caestecker

Year 2007, Volume 9, Issue 7

Abstract

WilmsÂ’ tumors, or nephroblastomas, are thought to arise from abnormal post-natal retention and dysregulated differentiation of nephrogenic progenitor cells that originate as the condensed metanephric mesenchyme of the embryonic kidney. We have previously shown that the transcriptional regulator CITED1 is expressed exclusively in these nephrogenic progenitor cells, and is down-regulated as they differentiate to form nephronic epithelia. In the current studies, we show that CITED1 expression persists in blastemal cell populations of both experimental rat nephroblastomas and human WilmsÂ’ tumors, and that primary human WilmsÂ’ tumors presenting with disseminated disease show the highest level of CITED1 expression. Unlike the predominantly cytoplasmic subcellular localization of CITED1 in the normal developing kidney, CITED1 is clearly detectable in the nuclear compartment of WilmsÂ’ tumor blastema. These findings indicate that CITED1 is a marker of primitive blastema in WilmsÂ’ tumors and suggest that persistent expression and/or altered subcellular localization of CITED1 in the condensed metanephric mesenchyme could play a role in WilmsÂ’ tumor initiation and pathogenesis.

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