Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium

Tcf-4 is a member of the Tcf/Lef family of transcription factors that inter act functionally with beta-catenin to mediate Wnt signaling in vertebrates. We have previously demonstrated that the tumor suppressor function of APC in the small intestine is mediated via regulation of Tcf-4/beta-catenin tra nscriptional activity. To gain further insight into the role of Tcf-4 in de velopment and carcinogenesis we have generated several mouse monoclonal ant ibodies, one of which is specific for Tcf-4 and another of which recognizes both Tcf-3 and Tcf-4. Immunohistochemistry performed with the Tcf 4-specif ic monoclonal antibody revealed high levels of expression in normal intesti nal and mammary epithelium and carcinomas derived therefrom, Additional sit es of Tcf-3 expression, as revealed by staining with the Tcf-3/-4 antibody, occurred only within the stomach epithelium, hair follicles, and keratinoc ytes of the skin. A temporal Tcf-4 expression gradient was observed along t he crypt-villus axis of human small intestinal epithelium: strong Tcf-4. ex pression was present within the crypts of early (week 16) human fetal small intestine, with the villi showing barely detectable Tcf-4 protein levels, Tcf-4 expression levels increased dramatically on the villi of more highly developed (week 22) fetal small intestine. We conclude that Tcf-4 exhibits a highly restricted expression pattern related to the developmental stage o f the intestinal epithelium, The high levels of Tcf-4 expression in mammary epithelium and mammary carcinomas may also indicate a role in the developm ent of this tissue and breast carcinoma.