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cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene

Khan, J; Bittner, M L; Saal, Lao LU ; Teichmann, U; Azorsa, D O; Gooden, G C; Pavan, W J; Trent, J M and Meltzer, P S (1999) In Proceedings of the National Academy of Sciences 96(23). p.13264-13269
Abstract
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 of PAX3, a developmental transcription factor required for limb myogenesis, with FKHR, a member of the forkhead family of transcription factors. The resultant PAX3-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, both Pax3 and PAX3-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... (More)
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 of PAX3, a developmental transcription factor required for limb myogenesis, with FKHR, a member of the forkhead family of transcription factors. The resultant PAX3-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, both Pax3 and PAX3-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 factors MyoD, 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 gene Igf2 and its binding protein Igfbp5. 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. (Less)
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author
publishing date
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publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
96
issue
23
pages
13264 - 13269
publisher
National Acad Sciences
external identifiers
  • pmid:10557309
  • scopus:0033539498
ISSN
1091-6490
language
English
LU publication?
no
id
bebcbe8b-9d00-48e9-8516-567999404141 (old id 1115298)
alternative location
http://www.pnas.org/content/96/23/13264.full
date added to LUP
2008-07-07 16:56:32
date last changed
2017-10-29 03:27:01
@article{bebcbe8b-9d00-48e9-8516-567999404141,
  abstract     = {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 of PAX3, a developmental transcription factor required for limb myogenesis, with FKHR, a member of the forkhead family of transcription factors. The resultant PAX3-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, both Pax3 and PAX3-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 factors MyoD, 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 gene Igf2 and its binding protein Igfbp5. 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.},
  author       = {Khan, J and Bittner, M L and Saal, Lao and Teichmann, U and Azorsa, D O and Gooden, G C and Pavan, W J and Trent, J M and Meltzer, P S},
  issn         = {1091-6490},
  language     = {eng},
  number       = {23},
  pages        = {13264--13269},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene},
  volume       = {96},
  year         = {1999},
}