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

• Published in: Regulatory peptides 2010-12, Vol.165 (2), p.224-231
• Main Authors: Patel, Oneel, Marshall, Kathryn M., Bramante, Gianni, Baldwin, Graham S., Shulkes, Arthur
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Biological and medical sciences; Blotting, Western; C-terminal flanking peptide; Cell Line, Tumor; Cell Survival - drug effects; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Gastrins - chemistry; Humans; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; PI3-kinase-dependent pathway; Progastrin; Protein Precursors - chemistry; Signal Transduction - drug effects; Vertebrates: endocrinology
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/j.regpep.2010.08.005

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. ► The C-terminal flanking peptide of progastrin inhibits gastric cancer cell apoptosis. ► Apoptosis inhibition by CTFP is dependent on the PI3-kinase pathway. ► CTFP increases BcL-xL and phosphorylated-Bad while decreasing active caspase 3.