Inactivation of the Type II TGF-β Receptor in Colon Cancer Cells with Microsatellite Instability

American Association for the Advancement of Science (AAAS) - Tập 268 Số 5215 - Trang 1336-1338 - 1995
Sanford D. Markowitz1, Jing Wang2, Lois L. Myeroff1, Ramon Parsons3, Lu‐Zhe Sun2, James Lutterbaugh1, Robert S. Fan2, Elizabeth Zborowska1, Kenneth W. Kinzler3, Bert Vogelstein4,5,3, Michael G. Brattain2, James K. V. Willson1
1Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106, USA.
2Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo, OH 43699 USA
3Johns Hopkins University Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
4Howard Hughes Medical Institute
5Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA

Tóm tắt

Transforming growth factor-β (TGF-β) is a potent inhibitor of epithelial cell growth. Human colon cancer cell lines with high rates of microsatellite instability were found to harbor mutations in the type II TGF-β receptor (RII) gene. Eight such examples, due to three different mutations, were identified. The mutations were clustered within small repeated sequences in the RII gene, were accompanied by the absence of cell surface RII receptors, and were usually associated with small amounts of RII transcript. RII mutation, by inducing the escape of cells from TGF-β-mediated growth control, links DNA repair defects with a specific pathway of tumor progression.

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American Association for the Advancement of Science (AAAS)

Tập 268 Số 5215

1336-1338

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