Expression Profiling of EWS/FLI Identifies NKX2.2 As a Critical Target Gene in Ewing's Sarcoma

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2006 May 16

PMID 16697960

Citations 182

Authors

Richard Smith

Leah A Owen

Deborah J Trem

Jenny S Wong

Jennifer S Whangbo

Todd R Golub

Stephen L Lessnick

Affiliations

Soon will be listed here.

Abstract

Our understanding of Ewing's sarcoma development mediated by the EWS/FLI fusion protein has been limited by a lack of knowledge regarding the tumor cell of origin. To circumvent this, we analyzed the function of EWS/FLI in Ewing's sarcoma itself. By combining retroviral-mediated RNA interference with reexpression studies, we show that ongoing EWS/FLI expression is required for the tumorigenic phenotype of Ewing's sarcoma. We used this system to define the full complement of EWS/FLI-regulated genes in Ewing's sarcoma. Functional analysis revealed that NKX2.2 is an EWS/FLI-regulated gene that is necessary for oncogenic transformation in this tumor. Thus, we developed a highly validated transcriptional profile for the EWS/FLI fusion protein and identified a critical target gene in Ewing's sarcoma development.

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