Amplification of MDM2 inhibits MyoD-mediated myogenesis

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

Research output: Contribution to journalArticle

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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
DOIs
StatePublished - Jan 1 1996

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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