Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma.

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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Smith R,Owen LA,Trem DJ,Wong JS,Whangbo JS,Golub TR,Lessnick SL

doi

10.1016/j.ccr.2006.04.004

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

405-16

issue

5

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(06)00114-0

journal_volume

9

pub_type

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