Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability

Sanford Markowitz, Jing Wang, Lois Myeroff, Ramon Parsons, Luzhe Sun, James Lutterbaugh, Robert S. Fan, Elizabeth Zborowska, Kenneth W. Kinzler, Bert Vogelstein, Michael Brattain, James K.V. Willson

Research output: Contribution to journalArticlepeer-review

2075 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1336-1338
Number of pages3
JournalScience
Volume268
Issue number5215
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • General

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