The C-terminal flanking peptide (CTFP) of progastrin inhibits apoptosis via a PI3-kinase-dependent pathway.
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.
Patel
Oneel
O
Department of Surgery, University of Melbourne Austin Health, Melbourne, Victoria 3084, Australia.
Marshall
Kathryn M
KM
Bramante
Gianni
G
Baldwin
Graham S
GS
Shulkes
Arthur
A
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D005755:Gastrins / Q000737:chemistry*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011498:Protein Precursors / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*
D005755:Gastrins; D010446:Peptide Fragments; D011498:Protein Precursors; C013706:big gastrin; D019869:Phosphatidylinositol 3-Kinases