Receptor tyrosine kinases expressed in metastatic colon cancer

Authors

  • Rolf J. Craven,

    1. Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
    2. The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
    3. Departments of Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
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  • Lihui Xu,

    1. The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
    2. Departments of Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
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  • Timothy M. Weiner,

    1. The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
    2. Departments of Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
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  • Yih-Woei Fridell,

    1. The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
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  • Georgette A. Dent,

    1. Departments of Pathology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
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  • Sudhir Srivastava,

    1. National Cancer Institute, Bethesda, MD
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  • Brian Varnum,

    1. Amgen Corp., Thousand Oaks, CA, USA
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  • Edison T. Liu,

    1. Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
    2. The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
    3. Departments of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
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  • William G. Cance

    Corresponding author
    1. The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
    2. Departments of Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599
    • 3010 Old Clinic Bldg., CB 7210, University of North Carolina, Chapel Hill, NC, 27599, USA. Fax: (919) 966-6308
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Abstract

Using a PCR-based cloning technique, we have isolated a series of DNA fragments coding for tyrosine kinases that are expressed in a metastatic human colon tumor, and have subsequently analyzed their expression pattern at the protein level in human tumors. We identified both the α and the β forms of the platelet-derived growth factor receptor (PDGFR), axl and 8 other genes, including 3 cytoplasmic tyrosine kinases. To study their expression in human colon cancer, we performed Western blots of matched sets of normal tissues and of carcinomas from the same patient. These revealed that the α-PDGFR migrates predominantly as a 200-kDa band in 8/8 normal tissues, and as a 170-kDa band in 17/17 malignant tissues, as well as in colonic polyps, suggesting that expression of an isoform of this receptor may be a marker for the progression of colon cancer. Additional studies showed that the Axl receptor tyrosine kinase was expressed at 10-fold higher levels in a peritoneal metastatic nodule than in other normal and malignant tissues. Immunohistochemistry revealed Axl over-expression specifically in the malignant cells of the tumor. This indicates that over-expression and possibly a differential processing event of tyrosine kinase receptors may be involved in colon cancer, and that they are potential markers for the progression of this disease. © 1995 Wiley-Liss. Inc.

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