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- Title
Mutational analysis of the tyrosine phosphatome in colorectal cancers.
- Authors
Wang, Zhenghe; Shen, Dong; Parsons, D Williams; Bardelli, Alberto; Sager, Jason; Szabo, Steve; Ptak, Janine; Silliman, Natalie; Peters, Brock A; van der Heijden, Michiel S; Parmigiani, Giovanni; Yan, Hai; Wang, Tian-Li; Riggins, Greg; Powell, Steven M; Willson, James K V; Markowitz, Sanford; Kinzler, Kenneth W; Vogelstein, Bert; Velculescu, Victor E
- Abstract
Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.
- Publication
Science (New York, N.Y.), 2004, Vol 304, Issue 5674, p1164
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1096096