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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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Mast cells are an essential hematopoietic component for polyp development.
E. Gounaris, S. E. Erdman, C. Restaino, M. F. Gurish, D. S. Friend, F. Gounari, D. M. Lee, G. Zhang, J. N. Glickman, K. Shin, et al. (2007)
PNAS 104, 19977-19982
   Abstract »    Full Text »    PDF »
Calcyclin-Binding Protein Inhibits Proliferation, Tumorigenicity, and Invasion of Gastric Cancer.
X. Ning, S. Sun, L. Hong, J. Liang, L. Liu, S. Han, Z. Liu, Y. Shi, Y. Li, W. Gong, et al. (2007)
Mol. Cancer Res. 5, 1254-1262
   Abstract »    Full Text »    PDF »
Transcriptome Profile of Human Colorectal Adenomas.
J. Sabates-Bellver, L. G. Van der Flier, M. de Palo, E. Cattaneo, C. Maake, H. Rehrauer, E. Laczko, M. A. Kurowski, J. M. Bujnicki, M. Menigatti, et al. (2007)
Mol. Cancer Res. 5, 1263-1275
   Abstract »    Full Text »    PDF »
Sox17 and Sox4 Differentially Regulate {beta}-Catenin/T-Cell Factor Activity and Proliferation of Colon Carcinoma Cells.
D. Sinner, J. J. Kordich, J. R. Spence, R. Opoka, S. Rankin, S.-C. J. Lin, D. Jonatan, A. M. Zorn, and J. M. Wells (2007)
Mol. Cell. Biol. 27, 7802-7815
   Abstract »    Full Text »    PDF »
Activation of Hepatic Stem Cell Marker EpCAM by Wnt {beta}-Catenin Signaling in Hepatocellular Carcinoma.
T. Yamashita, A. Budhu, M. Forgues, and X. W. Wang (2007)
Cancer Res. 67, 10831-10839
   Abstract »    Full Text »    PDF »
Phosphatidylethanol Accumulation Promotes Intestinal Hyperplasia by Inducing ZONAB-Mediated Cell Density Increase in Response to Chronic Ethanol Exposure.
J. Pannequin, N. Delaunay, C. Darido, T. Maurice, P. Crespy, M. A. Frohman, M. S. Balda, K. Matter, D. Joubert, J.-F. Bourgaux, et al. (2007)
Mol. Cancer Res. 5, 1147-1157
   Abstract »    Full Text »    PDF »
Dual Role of {alpha}6beta4 Integrin in Epidermal Tumor Growth: Tumor-suppressive Versus Tumor-promoting Function.
K. Raymond, M. Kreft, J.-Y. Song, H. Janssen, and A. Sonnenberg (2007)
Mol. Biol. Cell 18, 4210-4221
   Abstract »    Full Text »    PDF »
WNT10B Functional Dualism: beta-Catenin/Tcf-dependent Growth Promotion or Independent Suppression with Deregulated Expression in Cancer.
H. Yoshikawa, K. Matsubara, X. Zhou, S. Okamura, T. Kubo, Y. Murase, Y. Shikauchi, M. Esteller, J. G. Herman, X. Wei Wang, et al. (2007)
Mol. Biol. Cell 18, 4292-4303
   Abstract »    Full Text »    PDF »
Real-time imaging of beta-catenin dynamics in cells and living mice.
S. Naik and D. Piwnica-Worms (2007)
PNAS 104, 17465-17470
   Abstract »    Full Text »    PDF »
The genetics of hereditary colon cancer.
A. K. Rustgi (2007)
Genes & Dev. 21, 2525-2538
   Abstract »    Full Text »    PDF »
The pattern of {beta}-catenin responsiveness within the mammary gland is regulated by progesterone receptor.
M. Hiremath, J. P. Lydon, and P. Cowin (2007)
Development 134, 3703-3712
   Abstract »    Full Text »    PDF »
High Cancer-Specific Expression of Mesothelin (MSLN) Is Attributable to an Upstream Enhancer Containing a Transcription Enhancer Factor Dependent MCAT Motif.
T. Hucl, J. R. Brody, E. Gallmeier, C. A. Iacobuzio-Donahue, I. K. Farrance, and S. E. Kern (2007)
Cancer Res. 67, 9055-9065
   Abstract »    Full Text »    PDF »
Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene.
K. Aoki and M. M. Taketo (2007)
J. Cell Sci. 120, 3327-3335
   Abstract »    Full Text »    PDF »
Giving APCmin tumours a SPARC.
A. Gregorieff and H. Clevers (2007)
Gut 56, 1341-1343
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