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Short Communication |
From the Department of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany
Most colorectal cancers have loss of function mutations in the adenomatosis polyposis coli (APC) tumor suppressor gene. This leads to accumulation of ß-catenin, which together with the DNA binding protein TCF-4 functions as a transcriptional activator. Recently defined target genes are c-myc and cyclin D1, linking the APC gene defect to the capacity for autonomous proliferation of colon tumors. Here we report the identification of the matrix metalloproteinase MMP-7 as another target gene of ß-catenin/TCF-4. MMP-7 is overexpressed in 80% of human colorectal cancers and known to be an important factor for early tumor growth, with a potential function also for later progression steps, like invasion and metastasis. Our results explain the high percentage of MMP-7 overexpression in colon tumors. Moreover they indicate that defects in the APC tumor suppressor gene may also have an influence on later steps of colon tumor progression.
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G. G. Chung, E. Provost, E. P. Kielhorn, L. A. Charette, B. L. Smith, and D. L. Rimm Tissue Microarray Analysis of {beta}-Catenin in Colorectal Cancer Shows Nuclear Phospho-{beta}-catenin Is Associated with a Better Prognosis Clin. Cancer Res., December 1, 2001; 7(12): 4013 - 4020. [Abstract] [Full Text] [PDF]
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F. Hlubek, A. Jung, N. Kotzor, T. Kirchner, and T. Brabletz Expression of the Invasion Factor Laminin {gamma}2 in Colorectal Carcinomas Is Regulated by {beta}-Catenin Cancer Res., November 1, 2001; 61(22): 8089 - 8093. [Abstract] [Full Text] [PDF]
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A. Jung, M. Schrauder, U. Oswald, C. Knoll, P. Sellberg, R. Palmqvist, G. Niedobitek, T. Brabletz, and T. Kirchner The Invasion Front of Human Colorectal Adenocarcinomas Shows Co-Localization of Nuclear {beta}-Catenin, Cyclin D1, and p16INK4A and Is a Region of Low Proliferation Am. J. Pathol., November 1, 2001; 159(5): 1613 - 1617. [Abstract] [Full Text] [PDF]
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H. Shiina, M. Igawa, S. Urakami, K. Shigeno, T. Yoneda, M. Terashima, M. Deguchi, L. Ribeiro-Filho, and R. Dahiya Alterations of {beta}- and {gamma}-Catenin in N-Butyl-N-(-4-hydroxybutyl)nitrosamine-induced Murine Bladder Cancer Cancer Res., October 1, 2001; 61(19): 7101 - 7109. [Abstract] [Full Text] [PDF]
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A. Stockinger, A. Eger, J. Wolf, H. Beug, and R. Foisner E-cadherin regulates cell growth by modulating proliferation-dependent {beta}-catenin transcriptional activity J. Cell Biol., September 17, 2001; 154(6): 1185 - 1196. [Abstract] [Full Text] [PDF]
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T. Brabletz, A. Jung, S. Reu, M. Porzner, F. Hlubek, L. A. Kunz-Schughart, R. Knuechel, and T. Kirchner Variable beta -catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment PNAS, August 28, 2001; 98(18): 10356 - 10361. [Abstract] [Full Text] [PDF]
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H. Fukushima, H. Yamamoto, F. Itoh, H. Nakamura, Y. Min, S. Horiuchi, S. Iku, S. Sasaki, and K. Imai Association of matrilysin mRNA expression with K-ras mutations and progression in pancreatic ductal adenocarcinomas Carcinogenesis, July 1, 2001; 22(7): 1049 - 1052. [Abstract] [Full Text] [PDF]
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Y. Naishiro, T. Yamada, A. S. Takaoka, R. Hayashi, F. Hasegawa, K. Imai, and S. Hirohashi Restoration of Epithelial Cell Polarity in a Colorectal Cancer Cell Line by Suppression of {beta}-catenin/T-Cell Factor 4-mediated Gene Transactivation Cancer Res., March 1, 2001; 61(6): 2751 - 2758. [Abstract] [Full Text]
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H. C. Crawford, B. Fingleton, M. D. Gustavson, N. Kurpios, R. A. Wagenaar, J. A. Hassell, and L. M. Matrisian The PEA3 Subfamily of Ets Transcription Factors Synergizes with {beta}-Catenin-LEF-1 To Activate Matrilysin Transcription in Intestinal Tumors Mol. Cell. Biol., February 15, 2001; 21(4): 1370 - 1383. [Abstract] [Full Text]
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M. Fujita, Y. Furukawa, Y. Nagasawa, M. Ogawa, and Y. Nakamura Down-Regulation of Monocyte Chemotactic Protein-3 by Activated {beta}-Catenin Cancer Res., December 1, 2000; 60(23): 6683 - 6687. [Abstract] [Full Text]
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T. Kirchner and T. Brabletz Patterning and Nuclear {beta}-Catenin Expression in the Colonic Adenoma-Carcinoma Sequence : Analogies with Embryonic Gastrulation Am. J. Pathol., October 1, 2000; 157(4): 1113 - 1121. [Abstract] [Full Text] [PDF]
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T. Brabletz, K. Herrmann, A. Jung, G. Faller, and T. Kirchner Expression of Nuclear {beta}-Catenin and c-myc Is Correlated with Tumor Size but Not with Proliferative Activity of Colorectal Adenomas Am. J. Pathol., March 1, 2000; 156(3): 865 - 870. [Abstract] [Full Text] [PDF]
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