mdm-2 gene amplification in 3T3-L1 preadipocytes

Steven J. Berberich, Vaughn Litteral, Lindsey D. Mayo, Dara Tabesh, David Morris

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21 Scopus citations

Abstract

In this study the regulation of the murine double minute-2 (mdm-2) gene was examined in NIH 3T3L1 preadipocytes. The 3T3-L1 cell line, under proper conditions, has the capacity to differentiate from fibroblasts into adipocytes [15]. A recent report demonstrated that mdm-2 overexpression could block myogenesis [12]. While examining the regulation of the mdm-2 gene during adipogenesis, it was discovered that 3T3-L1 cells possess a 36-fold elevation of mdm-2 mRNA relative to A31 cells, another immortalized Balb/c 3T3 fibroblast cell line that lacks the capacity to differentiate. Based on Southern blot analysis, the increase in mdm-2 mRNA was the result of a mdm-2 gene amplification. The level of Mdm-2 protein in undifferentiated 3T3-L1 cells was elevated relative to A31 fibroblasts and resulted from translation of mRNA transcripts initiating from the p53-independent P1 promoter. We also examined how mdm-2 and p53 levels changed as undifferentiated fibroblasts converted to adipocytes. While mdm-2 mRNA levels remained elevated, p53 mRNA, protein, and DNA-binding activity decreased. These results suggest that adipogenesis is unaffected by elevated Mdm-2 levels and that the overexpression of mdm-2 mRNA is predominantly p53 independent.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalDifferentiation
Volume64
Issue number4
DOIs
StatePublished - Jan 1 1999

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ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

Cite this

Berberich, S. J., Litteral, V., Mayo, L. D., Tabesh, D., & Morris, D. (1999). mdm-2 gene amplification in 3T3-L1 preadipocytes. Differentiation, 64(4), 205-212. https://doi.org/10.1046/j.1432-0436.1999.6440205.x