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Science 21 March 1997:
Vol. 275. no. 5307, pp. 1787 - 1790
DOI: 10.1126/science.275.5307.1787
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Reports

Activation of beta -Catenin-Tcf Signaling in Colon Cancer by Mutations in beta -Catenin or APC

Patrice J. Morin, * Andrew B. Sparks, * Vladimir Korinek, Nick Barker, Hans Clevers, Bert Vogelstein, Kenneth W. Kinzler †

Inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene initiates colorectal neoplasia. One of the biochemical activities associated with the APC protein is down-regulation of transcriptional activation mediated by beta -catenin and T cell transcription factor 4 (Tcf-4). The protein products of mutant APC genes present in colorectal tumors were found to be defective in this activity. Furthermore, colorectal tumors with intact APC genes were found to contain activating mutations of beta -catenin that altered functionally significant phosphorylation sites. These results indicate that regulation of beta -catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or beta -catenin.

P. J. Morin and B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
A. B. Sparks and K. W. Kinzler, Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
V. Korinek, N. Barker, H. Clevers, Department of Immunology, University Hospital, 35008 GA, Utrecht, The Netherlands.
*   These authors contributed equally to this work.

†   To whom correspondence should be addressed.

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K. Aoki and M. M. Taketo (2007)
J. Cell Sci. 120, 3327-3335
   Abstract »    Full Text »    PDF »
Oxidative Stress Antagonizes Wnt Signaling in Osteoblast Precursors by Diverting beta-Catenin from T Cell Factor- to Forkhead Box O-mediated Transcription.
M. Almeida, L. Han, M. Martin-Millan, C. A. O'Brien, and S. C. Manolagas (2007)
J. Biol. Chem. 282, 27298-27305
   Abstract »    Full Text »    PDF »
A functional role of Cdx2 in {beta}-catenin signaling during transdifferentiation in endometrial carcinomas.
M. Saegusa, M. Hashimura, T. Kuwata, M. Hamano, Y. Wani, and I. Okayasu (2007)
Carcinogenesis 28, 1885-1892
   Abstract »    Full Text »    PDF »
Thiazolidinediones Modulate the Expression of beta-Catenin and Other Cell-Cycle Regulatory Proteins by Targeting the F-Box Proteins of Skp1-Cul1-F-box Protein E3 Ubiquitin Ligase Independently of Peroxisome Proliferator-Activated Receptor {gamma}.
S. Wei, L.-F. Lin, C.-C. Yang, Y.-C. Wang, G.-D. Chang, H. Chen, and C.-S. Chen (2007)
Mol. Pharmacol. 72, 725-733
   Abstract »    Full Text »    PDF »
Cyclooxygenase-2 and Platelet-Derived Growth Factor Receptors as Potential Targets in Treating Aggressive Fibromatosis.
S. Signoroni, M. Frattini, T. Negri, E. Pastore, E. Tamborini, P. Casieri, M. Orsenigo, L. Da Riva, P. Radice, P. Sala, et al. (2007)
Clin. Cancer Res. 13, 5034-5040
   Abstract »    Full Text »    PDF »
Salmonella Effector AvrA Regulation of Colonic Epithelial Cell Inflammation by Deubiquitination.
Z. Ye, E. O. Petrof, D. Boone, E. C. Claud, and J. Sun (2007)
Am. J. Pathol. 171, 882-892
   Abstract »    Full Text »    PDF »
Expression of L1-CAM and ADAM10 in Human Colon Cancer Cells Induces Metastasis.
N. Gavert, M. Sheffer, S. Raveh, S. Spaderna, M. Shtutman, T. Brabletz, F. Barany, P. Paty, D. Notterman, E. Domany, et al. (2007)
Cancer Res. 67, 7703-7712
   Abstract »    Full Text »    PDF »
Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium.
P. Bastide, C. Darido, J. Pannequin, R. Kist, S. Robine, C. Marty-Double, F. Bibeau, G. Scherer, D. Joubert, F. Hollande, et al. (2007)
J. Cell Biol. 178, 635-648
   Abstract »    Full Text »    PDF »
Haploinsufficiency of Kruppel-Like Factor 4 Promotes Adenomatous Polyposis Coli Dependent Intestinal Tumorigenesis.
A. M. Ghaleb, B. B. McConnell, M. O. Nandan, J. P. Katz, K. H. Kaestner, and V. W. Yang (2007)
Cancer Res. 67, 7147-7154
   Abstract »    Full Text »    PDF »
Transcriptional network governing the angiogenic switch in human pancreatic cancer.
A. Abdollahi, C. Schwager, J. Kleeff, I. Esposito, S. Domhan, P. Peschke, K. Hauser, P. Hahnfeldt, L. Hlatky, J. Debus, et al. (2007)
PNAS 104, 12890-12895
   Abstract »    Full Text »    PDF »
WNTs in the Ovine Uterus: Potential Regulation of Periimplantation Ovine Conceptus Development.
K. Hayashi, R. C. Burghardt, F. W. Bazer, and T. E. Spencer (2007)
Endocrinology 148, 3496-3506
   Abstract »    Full Text »    PDF »
Docosahexaenoic acid induces proteasome-dependent degradation of {beta}-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2.
G. Calviello, F. Resci, S. Serini, E. Piccioni, A. Toesca, A. Boninsegna, G. Monego, F. O. Ranelletti, and P. Palozza (2007)
Carcinogenesis 28, 1202-1209
   Abstract »    Full Text »    PDF »
Lysophosphatidic Acid Facilitates Proliferation of Colon Cancer Cells via Induction of Kruppel-like Factor 5.
H. Zhang, A. Bialkowska, R. Rusovici, S. Chanchevalap, H. Shim, J. P. Katz, V. W. Yang, and C. C. Yun (2007)
J. Biol. Chem. 282, 15541-15549
   Abstract »    Full Text »    PDF »
Axin Inhibits Extracellular Signal-regulated Kinase Pathway by Ras Degradation via beta-Catenin.
S. H. Jeon, J.-Y. Yoon, Y.-N. Park, W.-J. Jeong, S. Kim, E.-H. Jho, Y.-J. Surh, and K.-Y. Choi (2007)
J. Biol. Chem. 282, 14482-14492
   Abstract »    Full Text »    PDF »
Subcellular Localization of the Spindle Proteins Aurora A, Mad2, and BUBR1 Assessed by Immunohistochemistry.
E. Burum-Auensen, P. M. De Angelis, A. R. Schjolberg, K. L. Kravik, M. Aure, and O. P. F. Clausen (2007)
J. Histochem. Cytochem. 55, 477-486
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Development of Gastric Tumors in ApcMin/+ Mice by the Activation of the {beta}-Catenin/Tcf Signaling Pathway.
H. Tomita, Y. Yamada, T. Oyama, K. Hata, Y. Hirose, A. Hara, T. Kunisada, Y. Sugiyama, Y. Adachi, H. Linhart, et al. (2007)
Cancer Res. 67, 4079-4087
   Abstract »    Full Text »    PDF »
Induction of inducible nitric oxide synthase: a protective mechanism in colitis-induced adenocarcinoma.
R. Zhang, A. Ma, S. J. Urbanski, and D.-M. McCafferty (2007)
Carcinogenesis 28, 1122-1130
   Abstract »    Full Text »    PDF »
Absence of Stabilizing Mutations of {beta}-Catenin Encoded by CTNNB1 Exon 3 in a Large Series of Sporadic Parathyroid Adenomas.
J. Costa-Guda and A. Arnold (2007)
J. Clin. Endocrinol. Metab. 92, 1564-1566
   Abstract »    Full Text »    PDF »


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