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

Metallomics 2015 Oct 25;7(10):1390-8. Epub 2015 Sep 25.

The Department of Surgery, University of Melbourne, Austin Health, Studley Rd, Heidelberg, Victoria 3084, Australia.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1039/c5mt00147aDOI Listing
October 2015

Publication Analysis

Top Keywords

zinc ions
16
gastrin promoter
16
gastrin gene
12
colon cancer
12
cancer cells
12
vitro vivo
8
activation gastrin
8
promoter zinc
8
sw480 colon
8
mapk pathway
8
human gastrin
8
gene promoter
8
gastrin
7
promoter
6
activation
5
zinc
5
luciferase reporter
4
engineer luciferase
4
endogenous human
4
stimulated phosphorylation
4

Similar Publications