Alteration of Gene Expression in Normal-Appearing Colon Mucosa of APC min Mice and Human Cancer Patients

Abstract

The expression of many genes is altered in colon cancer, but the roles of these genes in carcinogenesis are unclear. Using real-time quantitative PCR, we demonstrated that several genes previously implicated in human colon cancer undergo altered expression in the APC min mouse adenomatous polyp, a precursor of cancer, as well as in normal-appearing surrounding mucosa. The five genes that were most highly up-regulated in mouse polyp were also significantly up-regulated in polyp-free colon mucosa. Similar changes occurred in morphologically normal mucosa of surgical sections taken from human cancer patients, frequently extending to the margins. Thus, morphologically normal colon mucosa in APC min mice and in human cancer patients is not metabolically normal. Altered gene expression in this tissue does not appear to result from a field effect because there was no correlation between extent of altered regulation and distance from polyp or tumor. Our data suggest that alterations of expression levels of these genes may be an early event in carcinogenesis and a marker of risk for the development of colon cancer.

EP1–4 subtype, COX and PPARγ receptor expression in colorectal cancer in prediction of disease‐specific mortality

“…15,[36][37][38][39][40][41][42][43] Our present study demonstrates that average content of COX-2 transcripts was not altered in tumor tissue compared with normal colon tissue, but immunohistochemistry confirmed that COX-2 protein appeared in a majority of tumor epithelial cells compared to a lack in normal mucosa epithe- Calculations were performed on complete biochemical information from 72 patients of the 99 included patients. lium.…”

Spectroscopic Microvascular Blood Detection From the Endoscopically Normal Colonic Mucosa: Biomarker for Neoplasia Risk

“…For instance, the ubiquitous nature of field carcinogenesis is underscored by the ability of the rectal mucosa to predict proximal neoplasia through analysis of cellular markers (decreased apoptosis 6 and increased proliferation 5 ) and morphological markers (ACF 4 or adenomas 3 ). Furthermore, genomic (cyclooxygenase 2, osteopontin) 8 and immunohistochemical (e.g. cytochrome C oxidase subunit I) 19 markers showed no clear diminution with distance.…”

“…Several lines of evidence suggest that there are profound cellular (increased proliferation 5 and decreased apoptosis 6 ), biochemical (e.g. protein kinase C activity 7 ), genomic (microarray) 8 and proteomic 9 abnormalities in the histologically normal mucosa of patients harboring neoplasia. While this provides powerful corroboration of the field effect, these techniques lack the requisite performance characteristics for clinical use.…”

Knockdown of peroxisome proliferator-activated receptor-β induces less differentiation and enhances cell–fibronectin adhesion of colon cancer cells

“…Targeted deletion of adenomatous polyposis coli alleles reduces PPAR-b expression in mouse intestine (Reed et al, 2004). PPAR-b expressions in human colorectal cancers or intestinal polyps of adenomatous polyposis coli (min) mice are either unchanged or downregulated as compared with normal controls (Orner et al, 2003;Chen et al, 2004;Yang et al, 2006). Experiments that examined polyp formation in PPAR-b-null adenomatous polyposis coli (min) mice show either no effect (Barak et al, 2002) or, paradoxically, an increase in polyp number and size compared with wild-type mice .…”