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Issue 10, 2015
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Activation by zinc of the human gastrin gene promoter in colon cancer cells in vitro and in vivo

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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 Gastluc 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.

Graphical abstract: Activation by zinc of the human gastrin gene promoter in colon cancer cells in vitro and in vivo

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The article was received on 05 Jun 2015, accepted on 07 Sep 2015 and first published on 14 Sep 2015


Article type: Paper
DOI: 10.1039/C5MT00147A
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Citation: Metallomics, 2015,7, 1390-1398
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    Activation by zinc of the human gastrin gene promoter in colon cancer cells in vitro and in vivo

    K. M. Marshall, M. Laval, O. Estacio, D. F. Hudson, P. Kalitsis, A. Shulkes, G. S. Baldwin and O. Patel, Metallomics, 2015, 7, 1390
    DOI: 10.1039/C5MT00147A

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