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 language | English (US) |
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Pages (from-to) | 5048-5057 |
Number of pages | 10 |
Journal | Molecular and cellular biology |
Volume | 16 |
Issue number | 9 |
DOIs | |
State | Published - 1996 |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology