Glycine-extended gastrin inhibits apoptosis in colon cancer cells via separate activation of Akt and JNK pathways

Beales, Ian L P and Ogunwobi, O (2006) Glycine-extended gastrin inhibits apoptosis in colon cancer cells via separate activation of Akt and JNK pathways. Molecular and Cellular Endocrinology, 247 (1-2). pp. 140-149.

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Abstract

Glycine-extended gastrin (G-Gly) is produced by colon cancers and has growth promoting and anti-apoptotic effects in the colonic epithelium. We have examined the anti-apoptotic effects of G-Gly and the signal transduction pathways involved. G-Gly stimulated HT-29 cell proliferation in a concentration dependent manner and inhibited serum-starvation and celecoxib-induced apoptosis. Inhibition of signalling via c-Jun NH2-terminal kinase (JNK) with SP600125 or PI3-kinase/Akt with LY294002 abolished the effects of G-Gly. G-Gly significantly increased phosphorylation of both JNK and Akt. The JAK2 inhibitor AG490 abolished the anti-apoptotic effect of G-Gly and inhibited phosphorylation of Akt but not of JNK. G-Gly stimulated tyrosine phosphorylation of JAK2. G-Gly-increased activation of AP-1 was JNK-dependant and activation of STAT3 was JAK2-dependant. We conclude that G-Gly promotes growth and inhibits apoptosis in colon cancer cells. These effects are mediated via the JAK2, PI3-kinase/Akt and JNK pathways. Activation of JAK2 is upstream of Akt but not of JNK.

Item Type: Article
Uncontrolled Keywords: anthracenes,apoptosis,cell line, tumor,cell survival,chromones,colonic neoplasms,gastrins,humans,jnk mitogen-activated protein kinases,janus kinase 2,morpholines,phosphatidylinositol 3-kinases,phosphorylation,protein-tyrosine kinases,proto-oncogene proteins,proto-oncogene proteins c-akt,pyrazoles,stat3 transcription factor,signal transduction,sulfonamides,transcription factor ap-1,tyrosine,tyrphostins
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
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Depositing User: EPrints Services
Date Deposited: 25 Nov 2010 11:09
Last Modified: 25 Jul 2018 06:04
URI: https://ueaeprints.uea.ac.uk/id/eprint/12183
DOI: 10.1016/j.mce.2005.12.050

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