1. ¹Section of Gastroenterology, Boston University School of Medicine, Boston Medical Center, 650 Albany Street, Boston, MA 02118, USA
2. ²Department of Oncology and the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA

Correspondence: Dr M Michael Wolfe, E-mail: michael.wolfe@bmc.org

Received 11 October 2004; Revised 27 January 2005; Accepted 11 February 2005; Published online 29 March 2005.

Abstract

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 -catenin oncoprotein. We thus sought to determine whether gastrin might regulate -catenin expression in colorectal tumour cells. Amidated gastrin-17 (G-17), one of the major circulating forms of gastrin, not only enhanced -catenin protein expression, but also one of its target genes, cyclin D1. Furthermore, activation of -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 _1/2 of -catenin protein, demonstrating that gastrin appears to exert its mitogenic effects on colorectal tumour cells, at least in part, by stabilising -catenin.