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ToolsOgunwobi, Olorunseun Olatunji and Beales, Ian L. P. (2006) Glycine-extended gastrin stimulates proliferation and inhibits apoptosis in colon cancer cells via cyclo-oxygenase-independent pathways. Regulatory Peptides, 134 (1). pp. 1-8. ISSN 1873-1686
Full text not available from this repository. (Request a copy)Abstract
Glycine-extended gastrin (G-Gly) is an end product of processing of the progastrin precursor peptide that has a different spectrum of activity to amidated gastrin. G-Gly promotes cell proliferation in normal and malignant colonic epithelium but the mechanisms responsible are poorly understood. Prostaglandins produced by the cyclo-oxygenase (COX) enzymes have been implicated as downstream mediators of several growth factors, and COX inhibitors such as non-steroidal anti-inflammatory drugs inhibit the proliferation and invasiveness of colonic cancer and reduce the incidence of colon cancer. We have examined the mechanisms of the actions of G-Gly in HT-29 colon cancer cells. G-Gly induced a dose-dependent increase in cell proliferation that was insensitive to inhibition of either COX-1 or COX-2, but was abolished by inhibition of the p38 MAP kinase, ERK and NF-κB pathways. G-Gly did not increase prostaglandin E2 production. Celecoxib induced apoptosis and reduced viable cell numbers in a COX-independent manner. G-Gly significantly reduced serum-starvation and celecoxib-induced apoptosis and this effect was also blocked by inhibition of the p38 MAP kinase, ERK and NF-κB pathways. Stimulation of HT-29 cells with G-Gly led to a rapid increase in ERK and p38 MAP kinase phosphorylation and increased nuclear translocation of active NF-κB. Activation of NF-κB was independent of ERK and p38 MAP kinase. G-Gly stimulates proliferation and inhibits apoptosis in colon cancer cells via COX-independent and ERK-, p38 MAP kinase-, and NF-κB-dependant pathways. Locally and systemically produced G-Gly may be important in reducing the beneficial effects of chemopreventative agents in colon cancer.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology |
| Depositing User: | EPrints Services |
| Date Deposited: | 25 Nov 2010 11:10 |
| Last Modified: | 13 Feb 2023 12:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/13384 |
| DOI: | 10.1016/j.regpep.2005.08.002 |
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