Gastrin stabilises beta-catenin protein in mouse colorectal cancer cells.
As gastrin may play a role in the pathophysiology of gastrointestinal (GI) malignancies, the elucidation of the mechanisms governing gastrin-induced proliferation has recently gained considerable interest. Several studies have reported that a large percentage of colorectal tumours overexpress or stabilise the beta-catenin oncoprotein. We thus sought to determine whether gastrin might regulate beta-catenin expression in colorectal tumour cells. Amidated gastrin-17 (G-17), one of the major circulating forms of gastrin, not only enhanced beta-catenin protein expression, but also one of its target genes, cyclin D1. Furthermore, activation of beta-catenin-dependent transcription by gastrin was confirmed by an increase in LEF-1 reporter activity, as well as enhanced cyclin D1 promoter activity. Finally, G-17 prolonged the tau(1/2) of beta-catenin protein, demonstrating that gastrin appears to exert its mitogenic effects on colorectal tumour cells, at least in part, by stabilising beta-catenin.
Song
D H
DH
Section of Gastroenterology, Boston University School of Medicine, Boston Medical Center, 650 Albany Street, Boston, MA 02118, USA.
Kaufman
J C
JC
Borodyansky
L
L
Albanese
C
C
Pestell
R G
RG
Wolfe
M Michael
MM
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D019938:Cyclin D1 / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D005755:Gastrins; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1; C013550:gastrin 17