Serum- and glucocorticoid-regulated kinase 1 (SGK1) induction by the EWS/NOR1(NR4A3) fusion protein Journal Article


Authors: Poulin, H.; Filion, C.; Ladanyi, M.; Labelle, Y.
Article Title: Serum- and glucocorticoid-regulated kinase 1 (SGK1) induction by the EWS/NOR1(NR4A3) fusion protein
Abstract: The NR4A3 nuclear receptor (also known as NOR1) is involved in tumorigenesis by the t(9;22) chromosome translocation encoding the EWS/NOR1 fusion protein found in approximately 75% of all cases of extraskeletal myxoid chondrosarcomas (EMC). Several observations suggest that one role of EWS/NOR1 in tumorigenesis may be to deregulate the expression of specific target genes. We have shown previously that constitutive expression of EWS/NOR1 in CFK2 fetal rat chondrogenic cells induces their transformation as measured by growth beyond confluency and growth in soft agar. To identify genes regulated by the fusion protein in this model, we have generated a CFK2 cell line in which the expression of EWS/NOR1 is controlled by tetracycline. Using the differential display technique, we have identified the serum- and glucocorticoid-regulated kinase 1 (SGK1) mRNA as being up-regulated in the presence of EWS/NOR1. Co-immunocytochemistry confirmed over-expression of the SGK1 protein in cells expressing EWS/NOR1. Significantly, immunohistochemistry of 10 EMC tumors positive for EWS/NOR1 showed that all of them over-express the SGK1 protein in contrast to non-neoplastic cells in the same biopsies and various other sarcoma types. These results strongly suggest that SGK1 may be a genuine in vivo target of EWS/NOR1 in EMC. © 2006 Elsevier Inc. All rights reserved.
Keywords: controlled study; protein expression; bone neoplasms; unclassified drug; dna-binding proteins; nonhuman; protein function; animal cell; animals; gene expression; cell growth; culture medium; cell line; nerve tissue proteins; tumor biopsy; proteomics; carcinogenesis; tissue section; regulatory mechanism; hybrid protein; recombinant fusion proteins; cell culture; messenger rna; immunocytochemistry; cell transformation; protein-serine-threonine kinases; rat; protein induction; rats; upregulation; up-regulation; tetracycline; rna binding protein ews; extraskeletal myxoid chondrosarcoma; serum and glucocorticoid regulated kinase 1; chondrosarcoma; immediate-early proteins; enzyme induction; rna-binding protein ews; genetic regulation; promoter regions (genetics); sgk1; cfk2 cells; ews/nor1; protein nor1
Journal Title: Biochemical and Biophysical Research Communications
Volume: 346
Issue: 1
ISSN: 0006-291X
Publisher: Elsevier Science, Inc.  
Date Published: 2006-07-21
Start Page: 306
End Page: 313
Language: English
DOI: 10.1016/j.bbrc.2006.05.134
PUBMED: 16756948
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 7" - "Export Date: 4 June 2012" - "CODEN: BBRCA" - "Source: Scopus"
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  1. Marc Ladanyi
    1326 Ladanyi