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Gastrokine 1 is abundantly and specifically expressed in superficial gastric epithelium, down-regulated in gastric carcinoma, and shows high evolutionary conservation

Authors

  • Karin A Oien,

    Corresponding author
    1. Cancer Research UK Department of Medical Oncology, Cancer Research UK Beatson Laboratories, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK
    2. University Department of Pathology, Glasgow Royal Infirmary, 84 Castle Street, Glasgow, G4 0SF, UK
    • Cancer Research UK Department of Medical Oncology, Cancer Research UK Beatson Laboratories, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD UK.
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  • Fiona McGregor,

    1. Cancer Research UK Department of Medical Oncology, Cancer Research UK Beatson Laboratories, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK
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  • Sharlene Butler,

    1. University Department of Pathology, Glasgow Royal Infirmary, 84 Castle Street, Glasgow, G4 0SF, UK
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  • Rod K Ferrier,

    1. University Department of Pathology, Glasgow Royal Infirmary, 84 Castle Street, Glasgow, G4 0SF, UK
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  • Ian Downie,

    1. University Department of Pathology, Glasgow Royal Infirmary, 84 Castle Street, Glasgow, G4 0SF, UK
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  • Steven Bryce,

    1. Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK
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  • Sharon Burns,

    1. Cancer Research UK Department of Medical Oncology, Cancer Research UK Beatson Laboratories, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK
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  • W Nicol Keith

    1. Cancer Research UK Department of Medical Oncology, Cancer Research UK Beatson Laboratories, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK
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Abstract

Through previous large-scale gene expression profiling we identified a transcript that was abundant in normal stomach and down-regulated in gastric cancer. Genes expressed at similar levels included gastrin, MUC5 and pS2, which are important in gastric function. We aimed to characterise this candidate, gastrokine 1 (GKN1), at mRNA, DNA, protein and tissue levels. The gene was studied in human, mouse, rat and cow, and was highly conserved across these species. The mRNA transcripts averaged 750 bp in length. The human, mouse and rat genes all contained six exons spanning 6 kb, and were located on chromosomes 2, 6 and 4 respectively. The full-length translation products were 183–185 amino acids long, reducing to the mature protein of 18 kDa following signal peptide cleavage; these predictions were confirmed by Western blotting. Tagged gastrokine 1 yielded granular cytoplasmic staining with perinuclear accentuation, representing the Golgi apparatus, in keeping with secretion or expression on the extracellular surface. Gene expression in tissues was profiled extensively by Northern blotting, in situ hybridisation and immunohistochemistry. Gastrokine 1 was highly expressed in normal stomach, where it was located in the superficial/foveolar gastric epithelium, but was absent from gastric carcinomas. Outwith the stomach, gastrokine 1 was found only in epithelia showing gastric metaplasia eg Barrett's oesophagus, the ulcer-associated cell lineage and ovarian mucinous neoplasms. In conclusion, we have characterised gastrokine 1, previously known as CA11, AMP-18 or foveolin. Its abundance in, and specificity for, native or metaplastic gastric epithelium, down-regulation in gastric carcinoma and evolutionary conservation suggest that this gene is physiologically important in the stomach. The function of gastrokine 1 is unknown but a role in mucosal protection is postulated. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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