title: Gastrokine 1 is abundantly and specifically expressed in superficial gastric epithelium, down-regulated in gastric carcinoma, and shows high evolutionary conservation.
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.
authors.affiliation: Cancer Research UK Department of Medical Oncology, Cancer Research UK Beatson Laboratories, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK. koien@beatson.gla.ac.uk
authors.forename: Karin A
authors.initials: KA
authors.lastname: Oien
authors.forename: Fiona
authors.initials: F
authors.lastname: McGregor
authors.forename: Sharlene
authors.initials: S
authors.lastname: Butler
authors.forename: Rod K
authors.initials: RK
authors.lastname: Ferrier
authors.forename: Ian
authors.initials: I
authors.lastname: Downie
authors.forename: Steven
authors.initials: S
authors.lastname: Bryce
authors.forename: Sharon
authors.initials: S
authors.lastname: Burns
authors.forename: W Nicol
authors.initials: WN
authors.lastname: Keith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002417:Cattle; D003594:Cytoplasmic Granules / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D019143:Evolution, Molecular; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008934:Mitogens / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D036361:Peptide Hormones; D010455:Peptides; D011230:Precancerous Conditions / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013045:Species Specificity; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; C477000:GKN1 protein, human; D008934:Mitogens; D009363:Neoplasm Proteins; D036361:Peptide Hormones; D010455:Peptides; D012333:RNA, Messenger