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Originally published in Science Express on 11 October 2001
Science 9 November 2001:
Vol. 294. no. 5545, pp. 1343 - 1346
DOI: 10.1126/science.1065817

Reports

A Phosphatase Associated with Metastasis of Colorectal Cancer

Saurabh Saha, Alberto Bardelli,* Phillip Buckhaults, Victor E. Velculescu, Carlo Rago, Brad St. Croix, Katharine E. Romans, Michael A. Choti, Christoph Lengauer, Kenneth W. Kinzler,dagger Bert Vogelsteindagger

To gain insights into the molecular basis for metastasis, we compared the global gene expression profile of metastatic colorectal cancer with that of primary cancers, benign colorectal tumors, and normal colorectal epithelium. Among the genes identified, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in nonmetastatic tumors and normal colorectal epithelium. In 3 of 12 metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provide a new therapeutic target for these intractable lesions.

Howard Hughes Medical Institute, The Oncology Center, Department of Surgery, and Program in Cellular and Molecular Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
*   On leave from the University of Torino, Institute for Cancer Research, 10060 Candiolo, Torino, Italy.

dagger    To whom correspondence should be addressed. E-mail: kinzlke{at}jhmi.edu (K.W.K.); vogelbe{at}welch.jhu.edu (B.V.)


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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
.
(2002)
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