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

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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

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