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Science 17 September 1999:
Vol. 285. no. 5435, pp. 1923 - 1926
DOI: 10.1126/science.285.5435.1923
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Reports

Synergy Between Tumor Suppressor APC and the beta -Catenin-Tcf4 Target Tcf1

Jeroen Roose, 1* Gerwin Huls, 1* Moniek van Beest, 1* Petra Moerer, 1 Karin van der Horn, 1 Roel Goldschmeding, 3 Ton Logtenberg, 1 Hans Clevers 12dagger

Mutations in APC or beta -catenin inappropriately activate the transcription factor Tcf4, thereby transforming intestinal epithelial cells. Here it is shown that one of the target genes of Tcf4 in epithelial cells is Tcf1. The most abundant Tcf1 isoforms lack a beta -catenin interaction domain. Tcf1-/- mice develop adenomas in the gut and mammary glands. Introduction of a mutant APC allele into these mice substantially increases the number of these adenomas. Tcf1 may act as a feedback repressor of beta -catenin-Tcf4 target genes and thus may cooperate with APC to suppress malignant transformation of epithelial cells.

1 Department of Immunology and
2 Center for Biomedical Genetics,
3 Department of Pathology, University Medical Center Utrecht, Post Office Box 85500, 3508 GA Utrecht, Netherlands.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: h.clevers{at}lab.azu.nl

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Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium.
S Naylor, M. Smalley, D Robertson, B. Gusterson, P. Edwards, and T. Dale (2000)
J. Cell Sci. 113, 2129-2138
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Cross-regulation of the Wnt signalling pathway: a role of MAP kinases.
J Behrens (2000)
J. Cell Sci. 113, 911-919
   Abstract »    PDF »
Mechanism of Chromatin Recognition and Transcriptional Regulation by LEF-1 and the Wnt/Wg-responsive LEF-1:{beta}-Catenin Complex.
A. TUTTER, G.S. MCALPINE, and K.A. JONES (1999)
Cold Spring Harb Symp Quant Biol 64, 445-452
   Abstract »    PDF »
Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of {beta}-catenin signaling.
H. G. Palmer, J. M. Gonzalez-Sancho, J. Espada, M. T. Berciano, I. Puig, J. Baulida, M. Quintanilla, A. Cano, A. G. de Herreros, M. Lafarga, et al. (2001)
J. Cell Biol. 154, 369-388
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Sequence-specific High Mobility Group Box Factors Recognize 10-12-Base Pair Minor Groove Motifs.
M. van Beest, D. Dooijes, M. van de Wetering, S. Kjaerulff, A. Bonvin, O. Nielsen, and H. Clevers (2000)
J. Biol. Chem. 275, 27266-27273
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Regulation of beta -Catenin Structure and Activity by Tyrosine Phosphorylation.
J. Piedra, D. Martinez, J. Castano, S. Miravet, M. Dunach, and A. G. de Herreros (2001)
J. Biol. Chem. 276, 20436-20443
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The Transcriptional Factor Tcf-4 Contains Different Binding Sites for beta -Catenin and Plakoglobin.
S. Miravet, J. Piedra, F. Miro, E. Itarte, A. Garcia de Herreros, and M. Dunach (2002)
J. Biol. Chem. 277, 1884-1891
   Abstract »    Full Text »    PDF »
Endogenous Protein Kinase CK2 Participates in Wnt Signaling in Mammary Epithelial Cells.
D. H. Song, D. J. Sussman, and D. C. Seldin (2000)
J. Biol. Chem. 275, 23790-23797
   Abstract »    Full Text »    PDF »
Activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias.
K. Miyoshi, J. M. Shillingford, F. Le Provost, F. Gounari, R. Bronson, H. von Boehmer, M. M. Taketo, R. D. Cardiff, L. Hennighausen, and K. Khazaie (2002)
PNAS 99, 219-224
   Abstract »    Full Text »    PDF »


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