Amplification of MDM2 inhibits MyoD-mediated myogenesis

Troy A. Fiddler, Leslie Smith, Stephen J. Tapscott, Mathew (Matt) Thayer

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

One obvious phenotype of tumor cells is the lack of terminal differentiation. We previously classified rhabdomyosarcoma cell lines as having either a recessive or a dominant nondifferentiating phenotype. To study the genetic basis of the dominant nondifferentiating phenotype, we utilized microcell fusion to transfer chromosomes from rhabdomyosarcoma cells into C2C12 myoblasts. Transfer of a derivative chromosome 14 inhibits differentiation. The derivative chromosome 14 contains a DNA amplification. MDM2 is amplified and overexpressed in these nondifferentiating hybrids and in the parental rhabdomyosarcoma. Forced expression of MDM2 inhibits MyoD- dependent transcription. Expression of antisense MDM2 restores MyoD- dependent transcriptional activity. We conclude that amplification and overexpression of MDM2 inhibit MyoD function, resulting in a dominant nondifferentiating phenotype.

Original languageEnglish (US)
Pages (from-to)5048-5057
Number of pages10
JournalMolecular and Cellular Biology
Volume16
Issue number9
StatePublished - 1996

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Muscle Development
Rhabdomyosarcoma
Phenotype
Chromosomes, Human, Pair 14
Myoblasts
Chromosomes
Cell Line
DNA
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Fiddler, T. A., Smith, L., Tapscott, S. J., & Thayer, M. M. (1996). Amplification of MDM2 inhibits MyoD-mediated myogenesis. Molecular and Cellular Biology, 16(9), 5048-5057.

Amplification of MDM2 inhibits MyoD-mediated myogenesis. / Fiddler, Troy A.; Smith, Leslie; Tapscott, Stephen J.; Thayer, Mathew (Matt).

In: Molecular and Cellular Biology, Vol. 16, No. 9, 1996, p. 5048-5057.

Research output: Contribution to journalArticle

Fiddler, TA, Smith, L, Tapscott, SJ & Thayer, MM 1996, 'Amplification of MDM2 inhibits MyoD-mediated myogenesis', Molecular and Cellular Biology, vol. 16, no. 9, pp. 5048-5057.
Fiddler, Troy A. ; Smith, Leslie ; Tapscott, Stephen J. ; Thayer, Mathew (Matt). / Amplification of MDM2 inhibits MyoD-mediated myogenesis. In: Molecular and Cellular Biology. 1996 ; Vol. 16, No. 9. pp. 5048-5057.
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