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We show here that Tcf4 haploinsufficiency results in colon tumor formation in a mouse tumor model that normally only develops small intestinal tumors. Further, we show that loss of Tcf4 early in development and in adult colon results in increased cell proliferation. These findings strongly suggest that Tcf4 normally modulates proliferation of the colonic epithelium and that disruption of Tcf4 activity increases proliferation, leading to colon tumorigenesis. Taken together, our in vivo studies favor a tumor suppressor function for Tcf4.<\/jats:p>","DOI":"10.1073\/pnas.1102300108","type":"journal-article","created":{"date-parts":[[2011,3,8]],"date-time":"2011-03-08T12:01:21Z","timestamp":1299585681000},"page":"4914-4919","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":105,"title":["T-cell factor 4 functions as a tumor suppressor whose disruption modulates colon cell proliferation and tumorigenesis"],"prefix":"10.1073","volume":"108","author":[{"given":"Melinda L.","family":"Angus-Hill","sequence":"first","affiliation":[{"name":"Department of Human Genetics, and"}]},{"given":"Kathryn M.","family":"Elbert","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, and"}]},{"given":"Julio","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, and"}]},{"given":"Mario R.","family":"Capecchi","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, and"},{"name":"The Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112"}]}],"member":"341","published-online":{"date-parts":[[2011,3,7]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1200\/JCO.2000.18.9.1967","article-title":"Biology of the adenomatous polyposis coli tumor suppressor","volume":"18","author":"Goss KH","year":"2000","unstructured":"KH Goss, J Groden, Biology of the adenomatous polyposis coli tumor suppressor. 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