Abstract
The majority of human colorectal cancers have elevated β-catenin/TCF regulated transcription due to either inactivating mutations of the APC tumor suppressor gene or activating mutations of β-catenin. Surprisingly, one commonly used colorectal cancer cell line was found to have intact APC and β-catenin and no demonstrable β-catenin/TCF regulated transcription. However, this line did possess a truncating mutation in one allele of CDX2, a gene whose inactivation has recently been shown to cause colon tumorigenesis in mice. Expression of CDX2 was found to be induced by restoring expression of wild type APC in a colorectal cancer cell line. These findings raise the intriguing possibility that CDX2 contributes to APC's tumor suppressive effects.
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Acknowledgements
This work was supported by NIH grants CA57345 and GM07814 and by a scholarship from the Fundação Luso-Americana para o Desenvolvimento (LT da Costa). B Vogelstein is an investigator of the Howard Hughes Medical Institutes. Genzyme Molecular Oncology (Genzyme) provided research support to KW Kinzler. B Vogelstein and KW Kinzler are consultants to Genzyme. The Johns Hopkins University and researchers (KW Kinzler and B Vogelstein) own Genzyme stock, which is subject to certain restrictions under University policy. The terms of this arrangement are being managed by the University in accordance with its conflict of interest policies.
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da Costa, L., He, TC., Yu, J. et al. CDX2 is mutated in a colorectal cancer with normal APC/β-catenin signaling. Oncogene 18, 5010–5014 (1999). https://doi.org/10.1038/sj.onc.1202872
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DOI: https://doi.org/10.1038/sj.onc.1202872
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