Colorectal Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 28, 2006; 12(12): 1859-1864
Published online Mar 28, 2006. doi: 10.3748/wjg.v12.i12.1859
Glycine-extended gastrin activates two independent tyrosine-kinases in upstream of p85/p110 phosphatidylinositol 3-kinase in human colonic tumour cells
Audrey Ferrand, Aline Kowalski-Chauvel, Julie Pannequin, Claudine Bertrand, Daniel Fourmy, Marlene Dufresne, Catherine Seva
Audrey Ferrand, Aline Kowalski-Chauvel, Claudine Bertrand, Daniel Fourmy, Marlene Dufresne, Catherine Seva, INSERM U.531, Groupe de Recherche de Biologie et Pathologie Digestives, IFR31, Institut Louis Bugnard, BP 84225, 31432 toulouse Cedex 4, France
Julie Pannequin, University of Melbourne Department of Surgery, Austin Campus, ARMC, Heidelberg, Victoria 3084, Australia
Supported by INSERM, the "Association pour la Recherche Contre le Cancer" Grants # 3664, # 4430, and the "Ligue Contre le Cancer"
Correspondence to: Catherine Seva, IFR31, Institut Louis Bugnard, BP 84225, Unité INSERM 531, Biologie et Pathologie Digestives, 31432 toulouse Cedex 4, France. sevac@toulouse.inserm.fr
Telephone: +33-5-61322408 Fax: +33-5-61322403
Received: September 13, 2005
Revised: October 2, 2005
Accepted: October 26, 2005
Published online: March 28, 2006
Abstract

AIM: To investigate whether Src, JAK2 and phosphatidylinositol 3-kinase (PI3K) pathways are involved in the proliferation of human colonic tumour cells induced by glycine-extended gastrin (G-gly), the precursor of the mature amidated gastrin and to elucidate the molecular interaction between these three kinases in response to this peptide.

METHODS: Using the human colonic tumour cell line HCT116 as a model, we first measured the activation of PI3K, p60-Src and JAK2 in response to G-gly by in vitro kinase assays. Then we investigated the involvement of these kinases in G-gly-induced cell proliferation by MTT test.

RESULTS: G-gly stimulation induced p60-Src, JAK2 and PI3K activation in HCT116. The different pathways were involved in proliferation of human colon cancer cells induced by G-gly. Furthermore, we found that both Src and JAK2 were necessary to PI3K regulation by this peptide. However, we did not find any cross-talk between the two tyrosine kinases.

CONCLUSION: Our results suggest that the p60-Src/PI3K and JAK2/PI3K pathways act independently to mediate G-gly proliferative effect on human colonic tumour cells.

Keywords: Colon cancer, Src, JAK2, Phosphatidylinositol 3-kinase, Glycine-extended gastrin