Cellular Expression Patterns of Genes Upregulated in Murine and Human Colonic Neoplasms

Abstract

Markers overexpressed in colonic tumors of the multiple intestinal neoplasia (Min) mouse have been recently identified by cDNA subtractive hybridization and by microarray analysis. The significance of such a marker depends on its expression in tumor vs stromal lineages and on its expression pattern in normal tissue. From 34 differentially expressed markers, 14 were found to be expressed from supporting lineages. The markers expressed in the tumor lineage were grouped into three classes on the basis of ISH in mouse models and IHC in human adenomas. The first class includes markers expressed both in neoplastic cells and in the proliferating cells residing at the bottom of normal colonic crypts. The second class of markers shows elevated expression in neoplastic cells and also in the postmitotic Paneth cells of the small intestine. Finally, the third class of marker shows detectable intestinal expression only within tumors but not in the normal intestinal epithelium. Is such a tumor-associated marker uniquely essential for tumor growth? Deficiency for the tumor-associated glycoprotein clusterin does not affect the multiplicity or growth rate of intestinal tumors in Min mice. Thus, clusterin is a candidate secreted colon cancer marker but not a single target for chemoprevention or therapy.