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Target disruption of the mutant β-catenin gene in colon cancer cell line HCT116: preservation of its malignant phenotype

Oncogene volume 21, pages 5906–5911 (2002)Cite this article

Abstract

Most colorectal carcinomas harbor genetic alterations that result in stabilization of β-catenin. A colorectal carcinoma cell line, HCT116, which has both mutated and wild-type β-catenin genes, was engineered by homologous recombination to investigate the significance of β-catenin gene mutation. As expected, the mutant allele-targeted clones showed decreased β-catenin expression and downregulation of T-cell factor (TCF)/lymphoid enhancer factor (LEF)-dependent transcription. Morphologically, targeted clones were only minimally altered under usual culture conditions, but under low serum conditions, mutant allele-targeted clones still grew in plane, in contrast to parental cell line and wild allele-targeted clones, which formed spheroids. The mutant allele-targeted clones showed no significant changes in growth rate and anchorage-independent growth in vitro, and displayed rather increased growth in vivo. Although β-catenin stabilization affects some biological characteristics including adhesive properties, it may not have growth-promoting effects at least in some colorectal carcinomas.

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Acknowledgements

We thank Drs Gen Fujii, Tesshi Yamada, Yasuyoshi Naishiro and Masaaki Takamura for technical advice. This work was supported in part by a Grant-in-Aid for Second Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare, and a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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  1. Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, 104-0045, Tokyo, Japan

    Shigeki Sekine, Tatsuhiro Shibata, Michiie Sakamoto & Setsuo Hirohashi

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  1. Shigeki Sekine
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  2. Tatsuhiro Shibata
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  3. Michiie Sakamoto
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Correspondence to Setsuo Hirohashi.

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Sekine, S., Shibata, T., Sakamoto, M. et al. Target disruption of the mutant β-catenin gene in colon cancer cell line HCT116: preservation of its malignant phenotype. Oncogene 21, 5906–5911 (2002). https://doi.org/10.1038/sj.onc.1205756

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