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Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H+-ATPase-like protein

Oncogene volume 21, pages 844–848 (2002)Cite this article

Abstract

ShIF is a bone marrow stroma cell-derived factor originally identified to support proliferation of bone marrow cells in vitro. This protein shares high sequence homology to the yeast vacuolar H+-ATPase subunit, Vph1p, and the 116 kDa proton pump of the rat and bovine synaptic vesicle, Vpp1. We examined the function of ShIF in the proliferation of human umbilical vein endothelial cells (HUVEC). ShIF inhibited HUVEC proliferation in a dose-dependent manner. Recombinant ShIF added at 10 and 20 ng/ml inhibited HUVEC proliferation by 21.6 and 44.3%, respectively and increasing the concentration of ShIF to 100 ng/ml inhibited proliferation by as much as 55.5%. When HUVEC cells were cultured at various concentrations of ShIF in the presence of anti-ShIF antibody, the inhibitory effects of ShIF to HUVEC proliferation were abrogated by 89–91% indicating that the activity of ShIF to HUVEC was specific. HUVEC cultured in the presence of ShIF and bafilomycin, a specific inhibitor of ATPase, resulted to a 90% growth inhibition. Thus, ShIF may act as an antagonist to the ATPase complex by disrupting the production of cellular ATP thereby decreasing the ability of HUVEC to proliferate.

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Acknowledgements

We thank Drs Y Hirata for HUVEC and C Schöenbach for valuable discussion and encouragement and M Yoshida for preparation of figures.

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Authors and Affiliations

  1. Chugai Research Institute for Molecular Medicine Incorporated, 153-2 Nagai, Niihari, 300-4101, Ibaraki, Japan

    Edgardo E Tulin, Nobuhisa Onoda, Masakazu Hasegawa & Hitoshi Nomura

  2. Department of Hematopoietic Factors, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108, Japan

    Edgardo E Tulin

  3. Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108, Japan

    Toshio Kitamura

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  1. Edgardo E Tulin
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  2. Nobuhisa Onoda
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  3. Masakazu Hasegawa
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Correspondence to Edgardo E Tulin.

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Tulin, E., Onoda, N., Hasegawa, M. et al. Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H+-ATPase-like protein. Oncogene 21, 844–848 (2002). https://doi.org/10.1038/sj.onc.1205114

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