The C-terminal flanking peptide (CTFP) of progastrin inhibits apoptosis via a PI3-kinase-dependent pathway

Regul Pept. 2010 Dec 10;165(2-3):224-31. doi: 10.1016/j.regpep.2010.08.005. Epub 2010 Aug 19.

Abstract

Progastrin is processed to a number of peptides including glycine-extended gastrin, amidated gastrin and the C-terminal flanking peptide (CTFP). Progastrin and gastrin-gly are pro-proliferative and anti-apoptotic in gastric and colorectal cancer cell lines. The CTFP is a major form of progastrin in the stomach and colon and stimulates proliferation. However the effect of CTFP on apoptosis has not been examined. Using the human gastric carcinoma cell line AGS we show that CTFP attenuates apoptosis through a PI3-kinase pathway by stimulating the phosphorylation of Akt leading to sustained increases in the concentrations of Bcl-xL and phosphorylated Bad protein and by reducing caspase 3 activity. The anti-apoptotic effect represents an important potential mechanism for the growth promoting action of CTFP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Flow Cytometry
  • Gastrins / chemistry*
  • Humans
  • Peptide Fragments / chemistry*
  • Peptide Fragments / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Precursors / chemistry*
  • Signal Transduction / drug effects*

Substances

  • Gastrins
  • Peptide Fragments
  • Protein Precursors
  • big gastrin
  • Phosphatidylinositol 3-Kinases