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The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth

C A Finlay1

  • 1Department of Molecular Biology, Princeton University, New Jersey 08544-1014.

Molecular and Cellular Biology
|January 1, 1993
PubMed

Insights

Murine double minute-2 (Mdm-2) overexpression immortalizes rat cells. Mdm-2 can overcome p53

Area of Science:

  • Oncogenes and Tumor Suppressors
  • Cellular Immortalization and Transformation
  • Gene Regulation and Cancer Biology

Background:

  • Mdm-2 (murine double minute-2) protein expression inhibits p53-mediated transactivation.
  • Overexpression of Mdm-2 can lead to cellular immortalization.
  • Mdm-2, in conjunction with an activated ras gene, can induce cellular transformation.

Purpose of the Study:

  • To investigate the role of Mdm-2 in cellular immortalization and transformation.
  • To determine the effect of wild-type p53 on Mdm-2-induced transformation.
  • To explore the interaction between Mdm-2, p53, and ras in cellular transformation.

Main Methods:

  • Transfection of primary rat embryo fibroblasts (REFs) with ras, mdm-2, and normal p53 genes.
  • Assessment of cellular immortalization and transformation phenotypes.
  • Analysis of p53 protein levels and characteristics in transformed cell lines.

Main Results:

  • Overexpression of Mdm-2 alone resulted in immortalization of REFs.
  • Co-expression of ras and mdm-2 led to transformation of REFs.
  • Transfection with ras, mdm-2, and wild-type p53 reduced transformation by 50%, with many resulting cell lines expressing functional p53.
  • Mdm-2 oncogene can overcome the growth-suppressive effects of wild-type p53.

Conclusions:

  • Mdm-2 possesses oncogenic properties, inducing immortalization and transformation.
  • Wild-type p53 does not completely inhibit transformation mediated by Mdm-2 and ras.
  • Mdm-2 can overcome the tumor-suppressive functions of p53, offering new insights into cancer development.

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