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Publication : T-cell factor 4 functions as a tumor suppressor whose disruption modulates colon cell proliferation and tumorigenesis.

First Author  Angus-Hill ML Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  12 Pages  4914-9
PubMed ID  21383188 Mgi Jnum  J:170088
Mgi Id  MGI:4943989 Doi  10.1073/pnas.1102300108
Citation  Angus-Hill ML, et al. (2011) T-cell factor 4 functions as a tumor suppressor whose disruption modulates colon cell proliferation and tumorigenesis. Proc Natl Acad Sci U S A 108(12):4914-9
abstractText  The Wnt/beta-catenin pathway plays multiple and diverse roles in development by regulating gene expression via T-cell factor/Lymphoid enhancer-binding factor (Tcf/Lef) DNA binding factors. Misregulation of this pathway is thought to initiate colon adenoma formation. It is controversial whether Tcf4 (Tcf7L2) functions as an oncogene or tumor suppressor gene in colon carcinogenesis. 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.
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