Identification of PAX3-FKHR-regulated genes differentially expressed between alveolar and embryonal rhabdomyosarcoma: Focus on MYCN as a biologically relevant target Journal Article
| Authors: | Mercado, G. E.; Xia, S. J.; Zhang, C.; Ahn, E. H.; Gustafson, D. M.; Lae, M.; Ladanyi, M.; Barr, F. G. |
| Article Title: | Identification of PAX3-FKHR-regulated genes differentially expressed between alveolar and embryonal rhabdomyosarcoma: Focus on MYCN as a biologically relevant target |
| Abstract: | Rhabdomyosarcoma is a family of myogenic soft tissue tumors subdivided into two main subtypes: alveolar (ARMS) and embryonal (ERMS). ARMS is characterized by a frequent 2; 13 chromosomal translocation that creates a PAX3-FKHR fusion transcription factor. To identify downstream targets of PAX3-FKHR, we introduced an inducible form of PAX3-FKHR into human RD ERMS cells. Microarray analysis identified 39 genes (29 upregulated and 10 downregulated) that are modulated by PAX3-FKHR in RD cells and differentially expressed between ERMS and PAX3-FKHR-positive ARMS tumors. Functional annotation demonstrated that genes involved in regulation of transcription and development, particularly neurogenesis, are represented in this group. MYCN was one notable neural-related transcription factor-encoding gene identified in this set, and its regulation by PAX3-FKHR was further confirmed at the RNA and protein levels. The findings of cycloheximide inhibition and time-course studies are consistent with the hypothesis that the PAX3-FKHR protein acts directly on the MYCN gene at the transcriptional level. Functional studies established that MYCN cooperates with PAX3-FKHR to enhance oncogenic activity. In conclusion, we identified a selected set of biologically relevant genes modulated by PAX3-FKHR, and demonstrated that PAX3-FKHR contributes to the expression of MYCN and in turn MYCN collaborates with PAX3-FKHR in tumorigenesis. © 2008 Wiley-Liss, Inc. |
| Keywords: | child; controlled study; human tissue; oncoprotein; human cell; genetics; comparative study; mouse; animal; metabolism; animals; mice; gene targeting; gene expression; gene expression profiling; nuclear protein; neoplasm proteins; transcription factor; gene function; genetic transcription; transcription, genetic; pathology; cell line, tumor; physiology; time; carcinogenesis; cell transformation, neoplastic; nuclear proteins; rna; gene expression regulation; gene expression regulation, neoplastic; biosynthesis; transcription regulation; hybrid protein; recombinant fusion proteins; messenger rna; rna, messenger; microarray analysis; oligonucleotide array sequence analysis; cell transformation; gene identification; oncogene proteins; tumor protein; tumor cell line; oncogene proteins, fusion; gene control; down regulation; upregulation; dna microarray; rna stability; transcription factor pax3; rhabdomyosarcoma; nervous system development; rna, neoplasm; cell strain 3t3; nih 3t3 cells; soft tissue neoplasms; soft tissue tumor; embryonal rhabdomyosarcoma; rhabdomyosarcoma, embryonal; downstream processing; pax3 fkhr fusion protein, human; pax3-fkhr fusion protein, human; rhabdomyosarcoma, alveolar; mycn protein, human; transcription factor fkhr; cycloheximide; protein synthesis inhibitor; transcription factor mycn; protein synthesis inhibitors |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 47 |
| Issue: | 6 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2008-06-01 |
| Start Page: | 510 |
| End Page: | 520 |
| Language: | English |
| DOI: | 10.1002/gcc.20554 |
| PUBMED: | 18335505 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 16" - "Export Date: 17 November 2011" - "CODEN: GCCAE" - "Source: Scopus" |
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