Please use this identifier to cite or link to this item:
https://ahro.austin.org.au/austinjspui/handle/1/12005
Title: | Zinc ions upregulate the hormone gastrin via an E-box motif in the proximal gastrin promoter. | Austin Authors: | Xiao, Lin;Kovac, Suzana;Chang, Mike;Shulkes, Arthur;Baldwin, Graham S;Patel, Oneel | Affiliation: | Department of Surgery, Austin Health, The University of Melbourne, Studley Road, Heidelberg, Victoria 3084, Australia | Issue Date: | 20-Dec-2013 | Publication information: | Journal of Molecular Endocrinology 2013; 52(1): 29-42 | Abstract: | Gastrin and its precursors act as growth factors for the normal and neoplastic gastrointestinal mucosa. As the hypoxia mimetic cobalt chloride upregulates the gastrin gene, the effect of other metal ions on gastrin promoter activity was investigated. Gastrin mRNA was measured by real-time PCR, gastrin peptides by RIA, and gastrin promoter activity by dual-luciferase reporter assay. Exposure to Zn(2)(+) ions increased gastrin mRNA concentrations in the human gastric adenocarcinoma cell line AGS in a dose-dependent manner, with a maximum stimulation of 55 ± 14-fold at 100 μM (P<0.05). Significant stimulation was also observed with Cd(2)(+) and Cu(2)(+), but not with Ca(2)(+), Mg(2)(+), Ni(2)(+), or Fe(3)(+) ions. Activation of MAPK and phosphatidylinositol 3-kinase pathways is necessary but not sufficient for gastrin induction by Zn(2)(+). Deletional mutation of the gastrin promoter identified an 11 bp DNA sequence, which contained an E-box motif, as necessary for Zn(2)(+)-dependent gastrin induction. The fact that E-box binding transcription factors play a crucial role in the epithelial-mesenchymal transition (EMT), together with our observation that Zn(2)(+) ions upregulate the gastrin gene in AGS cells by an E-box-dependent mechanism, suggests that Zn(2)(+) ions may induce an EMT, and that gastrin may be involved in the transition. | Gov't Doc #: | 24363439 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/12005 | DOI: | 10.1530/JME-13-0162 | Journal: | Journal of molecular endocrinology | URL: | https://pubmed.ncbi.nlm.nih.gov/24363439 | Type: | Journal Article | Subjects: | E-box MAPK PI3K cadmium cobalt gastrin iron promoter transcription zinc Animals Cadmium.pharmacology Cell Line, Tumor E-Box Elements Gastrins.genetics.metabolism Gene Expression Regulation.drug effects Humans Mice Mitogen-Activated Protein Kinases.metabolism Phosphatidylinositol 3-Kinases.metabolism Promoter Regions, Genetic Receptors, G-Protein-Coupled.metabolism Signal Transduction Transcriptional Activation.drug effects Zinc.pharmacology |
Appears in Collections: | Journal articles |
Show full item record
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.