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Science 21 March 1997:
Vol. 275. no. 5307, pp. 1784 - 1787
DOI: 10.1126/science.275.5307.1784
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Reports

Constitutive Transcriptional Activation by a beta -Catenin-Tcf Complex in APC-/- Colon Carcinoma

Vladimir Korinek, * Nick Barker, * Patrice J. Morin, Dick van Wichen, Roel de Weger, Kenneth W. Kinzler, Bert Vogelstein, Hans Clevers †

The adenomatous polyposis coli (APC) tumor suppressor protein binds to beta -catenin, a protein recently shown to interact with Tcf and Lef transcription factors. The gene encoding hTcf-4, a Tcf family member that is expressed in colonic epithelium, was cloned and characterized. hTcf-4 transactivates transcription only when associated with beta -catenin. Nuclei of APC-/- colon carcinoma cells were found to contain a stable beta -catenin-hTcf-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed beta -catenin from hTcf-4 and abrogated the transcriptional transactivation. Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.

V. Korinek, N. Barker, H. Clevers, Department of Immunology, University Hospital, Post Office Box B85500, 3508 GA Utrecht, Netherlands.
P. J. Morin and B. Vogelstein, Howard Hughes Medical Institute, Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
D. van Wichen and R. de Weger, Department of Pathology, University Hospital, 3508 GA Utrecht, Netherlands.
K. W. Kinzler, Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
*   These authors contributed equally to this study.

†   To whom correspondence should be addressed.

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Science. ISSN 0036-8075 (print), 1095-9203 (online)