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Title: Activation by zinc of the human gastrin gene promoter in colon cancer cells in vitro and in vivo
Austin Authors: Marshall, Kathryn M;Laval, Marie;Estacio, Ortis;Hudson, Damien F;Kalitsis, Paul;Shulkes, Arthur;Baldwin, Graham S;Patel, Oneel
Affiliation: Department of Surgery, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
Department of Paediatrics, The University of Melbourne, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia
Issue Date: Oct-2015
Date: 2015-09-15
Publication information: Metallomics 2015; 7(10): 1390-1398
Abstract: Over-expression of growth factors can contribute to the development and progression of cancer, and gastrins in particular have been implicated in accelerating the development of gastrointestinal cancers. Previously our group showed that hypoxia, cobalt chloride (a hypoxia mimetic) and zinc chloride could activate the expression of the gastrin gene in vitro. To characterise activation of the gastrin promoter by zinc ions further in vivo, TALEN technology was used to engineer a luciferase reporter construct into the endogenous human gastrin gene promoter in SW480 colon cancer cells. Gastrin promoter activity in the resultant Gast(luc) SW480 colon cancer cells was then measured by bioluminescence in cell culture and in tumour xenografts in SCID mice. Activation of intracellular signalling pathways was assessed by Western blotting. Activation of the gastrin promoter by zinc ions was concentration dependent in vitro and in vivo. Zinc ions significantly stimulated phosphorylation of ERK1/2 (MAPK pathway) but not of Akt (PI3K pathway). We conclude that the endogenous gastrin promoter is responsive to zinc ions, likely via activation of the MAPK pathway.
DOI: 10.1039/c5mt00147a
ORCID: 0000-0002-0944-8747
Journal: Metallomics
PubMed URL:
Type: Journal Article
Subjects: Colonic Neoplasms
Promoter Regions
Appears in Collections:Journal articles

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