Alternative phospholipase D/mTOR survival signal in human breast cancer cells

Oncogene. 2005 Jan 20;24(4):672-9. doi: 10.1038/sj.onc.1208099.


Cancer cells generate survival signals to suppress default apoptotic programs that protect from cancer. Phosphatidylinositol-3-kinase (PI3K) generates a survival signal that is frequently dysregulated in human cancers. Phospholipase D (PLD) has also been implicated in signals that promote survival. One of the targets of PLD signaling is mTOR (mammalian target of rapamycin), a critical regulator of cell cycle progression and cell growth. We report here that elevated PLD activity in the MDA-MB-231 human breast cancer cell line generates an mTOR-dependent survival signal that is independent of PI3K. In contrast, MDA-MB-435S breast cancer cells, which have very low levels of PLD activity, are dependent on PI3K for survival signals. The data presented here identify an alternative survival signal that is dependent on PLD and mTOR and is active in a breast cancer cell line where the PI3K survival pathway is not active.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Survival
  • Culture Media, Serum-Free / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phospholipase D / genetics
  • Phospholipase D / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinases / metabolism*
  • Signal Transduction*
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases


  • Culture Media, Serum-Free
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • phospholipase D2
  • Phospholipase D
  • Sirolimus