Identification of c- <i>MYC</i> as a Target of the APC Pathway
Tong‐Chuan HeT.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USAAndrew B. SparksT.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USACarlo RagoT.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USAHeiko HermekingT.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USALeigh ZawelT.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USALuís Teixeira da CostaT.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USAPatrice J. MorinT.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USABert VogelsteinT.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USAKenneth W. KinzlerT.-C. He, C. Rago, B. Vogelstein, Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. A. B. Sparks, H. Hermeking, L. Zawel, K. W. Kinzler, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. L. T. da Costa, Program in Human Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. P. J. Morin, National Institute on Aging, Baltimore, MD 21224, USA
1998en
ABI
Аннотация
The adenomatous polyposis coli gene (APC) is a tumor suppressor gene that is inactivated in most colorectal cancers. Mutations of APC cause aberrant accumulation of beta-catenin, which then binds T cell factor-4 (Tcf-4), causing increased transcriptional activation of unknown genes. Here, the c-MYC oncogene is identified as a target gene in this signaling pathway. Expression of c-MYC was shown to be repressed by wild-type APC and activated by beta-catenin, and these effects were mediated through Tcf-4 binding sites in the c-MYC promoter. These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers.
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