{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:54:54Z","timestamp":1790510094418,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,9,11]],"date-time":"2008-09-11T00:00:00Z","timestamp":1221091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The NR4A3 nuclear receptor is implicated in the development of extraskeletal myxoid chondrosarcoma (EMC), primitive sarcoma unrelated to conventional chondrosarcomas, through a specific fusion with EWSR1 resulting in an aberrant fusion protein that is thought to disrupt the transcriptional regulation of specific target genes. We performed an expression microarray analysis of EMC tumours expressing the EWSR1\/NR4A3 fusion protein, comparing their expression profiles to those of other sarcoma types. We thereby identified a set of genes significantly overexpressed in EMC relative to other sarcomas, including <jats:italic>PPARG<\/jats:italic> and <jats:italic>NDRG2<\/jats:italic>. Western blot or immunohistochemical analyses confirm that PPARG and NDRG2 are expressed in tumours positive for EWSR1\/NR4A3. Bioinformatic analysis identified a DNA response element for EWSR1\/NR4A3 in the <jats:italic>PPARG<\/jats:italic> promoter, and band\u2010shift experiments and transient transfections indicate that EWSR1\/NR4A3 can activate transcription through this element. Western blots further show that an isoform of the native NR4A3 receptor lacking the C\u2010terminal domain is very highly expressed in tumours positive for EWSR1\/NR4A3, and co\u2010transfections of this isoform along with EWSR1\/NR4A3 indicate that it may negatively regulate the activity of the fusion protein on the PPARG promoter. These results suggest that the overall expression of PPARG in EMC may be regulated in part by the balance between EWSR1\/NR4A3 and NR4A3, and that PPARG may play a crucial role in the development of these tumours. The specific up\u2010regulation of PPARG by EWSR1\/NR4A3 may also have potential therapeutic implications. Copyright \u00a9 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2445","type":"journal-article","created":{"date-parts":[[2008,9,11]],"date-time":"2008-09-11T10:08:12Z","timestamp":1221127692000},"page":"83-93","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["The EWSR1\/NR4A3 fusion protein of extraskeletal myxoid chondrosarcoma activates the <i>PPARG<\/i> nuclear receptor 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