dc.contributor.author | Li, Hongjie | |
dc.contributor.author | Smolen, Gromoslaw Aleksander | |
dc.contributor.author | Beers, Lisa F. | |
dc.contributor.author | Xia, Li | |
dc.contributor.author | Gerald, William | |
dc.contributor.author | Wang, Joanne | |
dc.contributor.author | Haber, Daniel Arie | |
dc.contributor.author | Lee, Sean Bong | |
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 |
dc.identifier.doi | 10.1371/journal.pone.0002353 | * |
dash.contributor.affiliated | Smolen, Gromoslaw Aleksander | |
dash.contributor.affiliated | Haber, Daniel | |