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[Cancer Research 60, 4761-4766, September 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Transactivation of the Multidrug Resistance 1 Gene by T-Cell Factor 4/ß-Catenin Complex in Early Colorectal Carcinogenesis1

Tesshi Yamada, Asako S. Takaoka, Yasuyoshi Naishiro, Reiko Hayashi, Keiji Maruyama, Chihaya Maesawa, Atsushi Ochiai and Setsuo Hirohashi2

Pathology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045 [T. Y., A. S. T., Y. N., R. H., K. M., C. M., S. H.], and Pathology Division, National Cancer Center Research Institute East, Kashiwa, Chiba 277-8577 [A. O.], Japan

The mutational inactivation of a tumor suppressor gene, adenomatous polyposis coli (APC), results in the accumulation of cytoplasmic ß-catenin protein and the activation of T-cell factor (TCF)/lymphoid enhancer factor transcriptional factors. A colorectal carcinoma cell line, DLD-1, was engineered to suppress transactivation by the TCF4/ß-catenin complex in a dominant-negative manner under the strict control of the tetracycline regulatory system. A large-scale comparison of the expression profiles, using two-color fluorescence hybridization of cDNA microarray, led to the identification of MDR1 as a target gene of the TCF4/ß-catenin complex. Luciferase reporter and gel retardation assays revealed the TCF4/ß-catenin responsive elements in the promoter of the human MDR1 gene. Corresponding to the accumulation of ß-catenin, expression of the MDR1 gene product was steadily up-regulated in adenomas and adenocarcinomas of 10 patients with familial adenomatous polyposis. In combination with cell proliferative activities of c-myc and cyclin D1, MDR1 may initiate colorectal tumorigenesis by suppressing cell death pathways programmed in intestinal epithelial cells.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2000 by the American Association for Cancer Research.