Dose-dependent inhibition of COX2 protein expression was found to

Dose-dependent inhibition of COX2 protein expression was found to be associated with reversal gene expression pattern changes in the colorectal normal-adenoma but less in the normal-carcinoma different pathway. Our findings can provide a molecular explanation with regard to the efficacy of selective COX2 inhibitors in CRC chemoprevention in the pre-cancerous adenoma phase. Furthermore, our results can give an insight into the global molecular background of selective COX2 inhibitor administration suggesting the involvement of p18-INK4C, CIP2 cyclin-dependent kinase inhibitors and p53-inducible BTG2 gene in NS398-dependent proliferation inhibition and TRAIL- and p53-mediated apoptotic pathways.

Supplementary Material Supplementary Figure 1: Click here for supplemental data(788K, tif) Supplementary Table 1: Click here for supplemental data(777K, xls) Supplementary information: Click here for supplemental data(20K, doc) Acknowledgments We thank Gabriella K��nya for preparing immunostainings and J��lia Ol��h for her help with western blotting. This study was supported in part by the National Office for Research and Technology, Hungary (GVOP-3.1.1-2004-0077/3.0 grant). Notes Supplementary Information accompanies the paper on British Journal of Cancer website (http://www.nature.com/bjc)
Regenerating gene (REG) family proteins are structurally similar proteins belonging to the calcium-dependent (C-type) lectin gene superfamily. In humans, the family has four known members; REGI��, REGI��, REGIII, and REGIV.

The first REG protein was discovered in regenerating pancreatic islets in rats [1], and REG proteins have since been found involved in other physiological and pathophysiological processes [2]. Their basic biological effects seem to be induction of cellular proliferation and inhibition of apoptosis. GSK-3 REGI�� seems to have a physiological role in the gastric mucosa, related to the general trophic effect of gastrin on the gastric oxyntic mucosa [3]. Elsewhere in the gastrointestinal system, these proteins are found during tissue injury and neoplasia. They are overexpressed in gastric and colorectal cancers [4], and in colorectal cancer cell lines [5]. Lawrance et al. [6] first showed overexpression of REGI�� and REGI�� mRNA in resected colonic tissue from both Crohn’s disease (CD) and ulcerative colitis (UC). Subsequent studies have found that REGI��, REGI�� and REGIII mRNAs are overexpressed in the colon in inflammatory bowel disease (IBD) [7,8] and that REGI�� is overexpressed in CD [9]. Sekikawa et al. found that REGI�� mRNA and protein are overexpressed in UC [10], in particular in dysplasia or cancer, and a more recent study also shows a possible role for REG1�� as a marker for UC associated neoplasia [11].

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