Mutant p53 in MDA-MB-231 breast cancer cells is stabilized by elevated phospholipase D activity and contributes to survival signals generated by phospholipase D

Oncogene. 2006 Nov 23;25(55):7305-10. doi: 10.1038/sj.onc.1209735. Epub 2006 Jun 19.


p53 is the most commonly mutated gene in human cancer. Although the loss of tumor suppressor functions for p53 in tumorigenesis is well characterized, gain-of-function p53 mutations observed in most cancers are not as widely appreciated. The human breast cancer cell line MDA-MB-231, which has high levels of a mutant p53, has high levels of phospholipase D (PLD) activity, which provides a survival signal in these cells when deprived of serum growth factors. We report here that the mutant p53 in MDA-MB-231 cells is stabilized by the elevated PLD activity in these cells. Surprisingly, the survival of MDA-MB-231 cells deprived of serum was dependent on the mutant p53. These data indicate that a mutant p53, stabilized by elevated PLD activity, can contribute to the suppression of apoptosis in a human breast cancer cell line and suggest a rationale for the selection of p53 mutations early in tumorigenesis to suppress apoptosis in an emerging tumor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Survival*
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Phospholipase D / metabolism*
  • Protein Kinases / metabolism
  • TOR Serine-Threonine Kinases
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism


  • Tumor Suppressor Protein p53
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • Phospholipase D