Adenosine Transporter ENT4 Is a Direct Target of EWS/WT1 Translocation Product and Is Highly Expressed in Desmoplastic Small Round Cell Tumor

Adenosine Transporter ENT4 Is a Direct Target of EWS/WT1 Translocation Product and Is Highly Expressed in Desmoplastic Small Round Cell Tumor

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Adenosine Transporter ENT4 Is a Direct Target of EWS/WT1 Translocation Product and Is Highly Expressed in Desmoplastic Small Round Cell Tumor

dc.contributor.author	Li, Hongjie
dc.contributor.author	Beers, Lisa F.
dc.contributor.author	Gerald, William
dc.contributor.author	Wang, Joanne
dc.contributor.author	Lee, Sean Bong
dc.contributor.author	Smolen, Gromoslaw Aleksander
dc.contributor.author	Xia, Li
dc.contributor.author	Haber, Daniel Arie
dc.date.accessioned	2011-02-07T16:54:25Z
dc.date.issued	2008
dc.identifier.citation	Li, Hongjie, Gromoslaw A. Smolen, Lisa F. Beers, Li Xia, William Gerald, Joanne Wang, Daniel A. Haber, and Sean Bong Lee. 2008. Adenosine Transporter ENT4 Is a Direct Target of EWS/WT1 Translocation Product and Is Highly Expressed in Desmoplastic Small Round Cell Tumor. PLoS ONE 3(6): e2353.	en_US
dc.identifier.issn	1932-6203	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:4706321
dc.description.abstract	Background: Desmoplastic Small Round Cell Tumor (DSRCT) is a highly aggressive malignancy that affects mainly adolescents and young adults. A defining characteristic of DSRCT is a specific chromosomal translocation, t(11;22)(p13;q12), that fuses EWS with WT1, leading to a production of two isoforms of chimeric transcription factor, EWS/WT1(−KTS) and EWS/WT1(+KTS). The chimeric proteins are thought to play critical roles in various stages of oncogenesis through aberrant transcription of different genes, but only a few of these genes have been identified. Methodology/Principal Findings: We report the identification of a new target of EWS/WT1, ENT4 (equilibrative nucleoside transporter 4) which encodes a pH-dependent adenosine transporter. ENT4 is transcriptionally activated by both isoforms of EWS/WT1 as evidenced by promoter-reporter and chromatin immunoprecipitation (ChIP) analyses. Furthermore, ENT4 is highly and specifically expressed in primary tumors of DSRCT as well as in a DSRCT cell line, JN-DSRCT-1. Treatment of JN-DSRCT-1 cells with adenosine analogs, such as 2-chloro-2′-deoxyadenosine (2-CdA), resulted in an increased cytotoxic response in dose- and pH-dependent manner. Conclusions/Significance: Our detailed analyses of a novel target of EWS/WT1 in DSRCT reveal an insight into the oncogenic mechanism of EWS-fusion chromosomal translocation gene products and provide a new marker for DSRCT. Furthermore, identification of ENT4 as a highly expressed transcript in DSRCT may represent an attractive pathway for targeting chemotherapeutic drugs into DSRCT.	en_US
dc.language.iso	en_US	en_US
dc.publisher	Public Library of Science	en_US
dc.relation.isversionof	doi:10.1371/journal.pone.0002353	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394657/pdf/	en_US
dash.license	LAA
dc.subject	biochemistry	en_US
dc.subject	transcription and translation	en_US
dc.subject	molecular biology	en_US
dc.subject	transcription initiation and activation	en_US
dc.subject	oncology	en_US
dc.subject	sarcomas	en_US
dc.title	Adenosine Transporter ENT4 Is a Direct Target of EWS/WT1 Translocation Product and Is Highly Expressed in Desmoplastic Small Round Cell Tumor	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	PLoS ONE	en_US
dash.depositing.author	Smolen, Gromoslaw Aleksander
dc.date.available	2011-02-07T16:54:25Z
dash.affiliation.other	HMS^Medicine-Massachusetts General Hospital	en_US
dash.affiliation.other	HMS^Medicine-Massachusetts General Hospital	en_US