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Effect of Gastrin and Anti-Gastrin Antibodies on Proliferation of Hepatocyte Cell Lines

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Abstract

Gastrin (G-17) and its precursor glycine-extended gastrin (G-17-gly) have been shown to be trophic to some gastrointestinal tumors. This in vitro study assessed the effect of G-17, G-17-gly, anti-gastrin antibodies (anti-G-17), and the CCK-B receptor antagonist PD135,158 on three hepatoma cell lines (PLC/PRF/5, HepG2 and MCA-RH7777) and an embryonic liver cell line (WRL68). The pancreatic adenocarcinoma cell line AR42J was used as a positive control. G-17 and G-17-gly caused significant proliferation of AR42J and WRL68 cell lines. G-17-gly but not G-17 induced significant proliferation of the PLC/PRF/5 cell line. Anti-G-17 and PD135,158 significantly inhibited unstimulated AR42J and WRL68 cell lines. Anti-G-17 also inhibited the proliferative effects of G-17 and G-17-gly on AR42J, WRL68, and PLC/PRF/5 cell lines, whereas PD135,158 inhibited the proliferative effect of G-17 only. G-17 and G-17-gly as well as anti-G-17 and PD135,158 had no effect on HepG2 and MCA-RH77777 cell lines. It is concluded that G-17-stimulated proliferation is mediated via the CCK-B receptor and G-17-gly via a separate, as yet uncharacterized, receptor. There may therefore be a role for gastrin in embryonic hepatocellular proliferation and perhaps also in the proliferation of some hepatocellular tumors.

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Authors and Affiliations

  1. Department of Medicine, Royal Free Hospital School, London

    Martyn Caplin, Kossar Khan, Kay Savage & Roy Pounder

  2. Department of Histopathology, Royal Free Hospital School, London

    Stephen Grimes & Dov Michaeli

  3. Aphton Corporation, Woodland, California

    Amar Dhillon

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  1. Martyn Caplin
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  2. Kossar Khan
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  4. Dov Michaeli
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  5. Kay Savage
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  6. Roy Pounder
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  7. Amar Dhillon
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Caplin, M., Khan, K., Grimes, S. et al. Effect of Gastrin and Anti-Gastrin Antibodies on Proliferation of Hepatocyte Cell Lines. Dig Dis Sci 46, 1356–1366 (2001). https://doi.org/10.1023/A:1010634031457

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