Authors: van der Woude C.J.¹; Kleibeuker J.H.²; Jansen P.L.M.²; Moshage H.²

Source: Apoptosis, Volume 9, Number 2, March 2004 , pp. 123-130(8)

Publisher: Springer

Abstract:

Inflammatory conditions are characterized by activation of the transcription factor nuclear factor kappa B (NF-B), resulting in the expression of NF-B-regulated, inflammation-related genes, such as inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2). Expression of these genes contributes to the survival of cells. Indeed, exposure to pro-inflammatory cytokines in the absence of NF-B activation leads to apoptosis.^1,2 Chronic inflammatory conditions are accompanied by constitutive activation of NF-B and hence, to the continuous expression of pro-survival genes, as has been observed in chronic gastritis.³ Although beneficial for the survival of cells during exposure to inflammatory stress, the continuous activation of NF-B may also pose a risk: cells with a pro-survival phenotype may give rise to continuously proliferating cells and may thus be tumorigenic. Progression to a malignant phenotype of these cells will most likely involve additional changes in the expression of non-NF-B regulated genes e.g. a shift in the balance of pro- and anti-apoptotic genes towards a more anti-apoptotic phenotype. Literature on inflammation-related genes and the apoptotic balance in pre-malignant and malignant conditions in the gastro-intestinal tract is still scarce and conflicting. In this review, we aim to give an overview of the existing literature and we will focus on inflammation- and apoptosis-related genes in the sequence of normal epithelium-inflamed epithelium-metaplasia-dysplasia-cancer in the gastrointestinal tract, in particular esophagus (Barrett's esophagus: BE), stomach (gastritis) and colon (inflammatory bowel disease: IBD).

Keywords: apoptosis; COX-2; gastro-intestinal tract; iNOS; NF-B

Document Type: Review article

DOI: http://dx.doi.org/10.1023/B:APPT.0000018794.26438.22

Affiliations: 1: Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands., Email: c.vanderwoude@erasmusmc.nl 2: Department of Gastroenterology and Hepatology, University Hospital Groningen, The Netherlands

Publication date: 2004-03-01

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