Open AccesscDNA microarrays detect activation of a myogenic transcription program by thePAX3-FKHRfusion oncogene
Author(s) -
Javed Khan,
Michael Bittner,
Lao H. Saal,
Ulrike Teichmann,
David O. Azorsa,
Gerald C. Gooden,
William J. Pavan,
Jeffrey M. Trent,
Paul S. Meltzer
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.23.13264
Subject(s) - pax3 , alveolar rhabdomyosarcoma , biology , transcription factor , myod , fusion gene , complementary dna , myogenesis , fusion protein , gene , gene expression , microbiology and biotechnology , oncogene , cancer research , genetics , rhabdomyosarcoma , medicine , sarcoma , pathology , recombinant dna , cell cycle
Alveolar rhabdomyosarcoma is an aggressive pediatric cancer of striated muscle characterized in 60% of cases by a t(2;13)(q35;q14). This results in the fusion ofPAX3 , a developmental transcription factor required for limb myogenesis, withFKHR , a member of the forkhead family of transcription factors. The resultantPAX3-FKHR gene possesses transforming properties; however, the effects of this chimeric oncogene on gene expression are largely unknown. To investigate the actions of these transcription factors, bothPax3 andPAX3-FKHR were introduced into NIH 3T3 cells, and the resultant gene expression changes were analyzed with a murine cDNA microarray containing 2,225 elements. We found that PAX3-FKHR but not PAX3 activated a myogenic transcription program including the induction of transcription factorsMyoD , Myogenin,Six1 , and Slug as well as a battery of genes involved in several aspects of muscle function. Notable among this group were the growth factor geneIgf2 and its binding proteinIgfbp5 . Relevance of this model was suggested by verification that three of these genes (IGFBP5 , HSIX1, and Slug) were also expressed in alveolar rhabdomyosarcoma cell lines. This study utilizes cDNA microarrays to elucidate the pattern of gene expression induced by an oncogenic transcription factor and demonstrates the profound myogenic properties of PAX3-FKHR in NIH 3T3 cells.