The p75(NTR) tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells

Biochem Biophys Res Commun. 2006 Mar 24;341(4):1184-92. doi: 10.1016/j.bbrc.2006.01.073. Epub 2006 Jan 26.


The p75 neurotrophin receptor (p75(NTR)) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75(NTR) retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted (DeltaDD) dominant-negative antagonist of p75(NTR) showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75(NTR)-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75(NTR) expressing cells occurred via the intrinsic mitochondrial pathway leading to a sequential caspase-9 and -7 cascade. Since the death domain deleted dominant-negative antagonist of p75(NTR) rescued intrinsic caspase associated apoptosis in PC-3 cells, this shows p75(NTR) was integral to ligand independent induction of apoptosis. Moreover, the ability of ligand to ameliorate the p75(NTR)-dependent intrinsic apoptotic cascade indicates that NGF functioned as a survival factor for p75(NTR) expressing prostate cancer cells.

MeSH terms

  • Apoptosis / drug effects
  • Caspases / physiology*
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Humans
  • In Situ Nick-End Labeling
  • Male
  • Nerve Growth Factor / pharmacology
  • Nerve Tissue Proteins / physiology*
  • Prostatic Neoplasms / physiopathology*
  • Receptors, Nerve Growth Factor / physiology*


  • NGFR protein, human
  • Nerve Tissue Proteins
  • Receptors, Nerve Growth Factor
  • Nerve Growth Factor
  • Caspases