title: 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.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10021, USA.
authors.forename: L
authors.initials: L
authors.lastname: Hui
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.forename: Y
authors.initials: Y
authors.lastname: Yan
authors.forename: J
authors.initials: J
authors.lastname: Bargonetti
authors.forename: D A
authors.initials: DA
authors.lastname: Foster
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D010739:Phospholipase D