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Expression of von Hippel–Lindau Protein in Normal and Pathological Human Tissues

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Abstract

To examine the localization of von Hippel–Lindau (VHL) protein in human tissues, we produced four novel monoclonal antibodies against human VHL protein. Western blot analysis revealed that two of these antibodies recognized the epitope in amino acid sequence 60–89 of the VHL protein and the others recognized sequences 54–60 and 189–213. In a wild-type VHL gene-transfected cell line, immunocytochemistry and immunoelectron microscopy demonstrated the intracytoplasmic localization of VHL protein, particularly in mitotic cells. In normal human tissues, VHL protein was detected immunohistochemically in epithelial cells covering the body surface and the alimentary, respiratory, and genitourinary tracts; in secretory epithelial cells of exocrine and endocrine organs; in parenchymal cells of visceral organs; in cardiomyocytes; in neurons in nervous tissue; in lymphocytes in lymphoid tissue; and in macrophages. In pathological specimens, VHL protein was expressed in VHL-related tumor, as well as in endothelial cells, fibroblasts, and pericytes, all of which are involved in active angiogenesis. These findings suggest that these monoclonal antibodies can be useful for various immunological assays and that the VHL protein plays fundamental roles in physiological and pathological situations, especially in neovascularization.

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Authors and Affiliations

  1. Second Department of Pathology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto o860-0811, Japan

    Naomi Sakashita, Motohiro Takeya & Kiyoshi Takahashi

  2. Department of Urology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan

    Takeshi Kishida

  3. Laboratory of Immunobiology, National Cancer Institute, National Cancer Institute-Frederick Cancer Research Facility and Development Center, Bldg. 560, Rm. 12-71, Frederick, MD, 21702, USA

    Thomas M. Stackhouse & Berton Zbar

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  1. Naomi Sakashita
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  2. Motohiro Takeya
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  3. Takeshi Kishida
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  4. Thomas M. Stackhouse
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  5. Berton Zbar
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  6. Kiyoshi Takahashi
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Sakashita, N., Takeya, M., Kishida, T. et al. Expression of von Hippel–Lindau Protein in Normal and Pathological Human Tissues. Histochem J 31, 133–144 (1999). https://doi.org/10.1023/A:1003554712386

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