| Autor: |
Brookes, M. J., Boult, J., Roberts, K., Cooper, B. T., Hotchin, N. A., Matthews, G., Iqbal, T., Tselepis, C. |
| Předmět: |
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| Zdroj: |
Oncogene; 2/7/2008, Vol. 27 Issue 7, p966-975, 10p, 9 Graphs |
| Abstrakt: |
There is an emerging body of evidence implicating iron in carcinogenesis and in particular colorectal cancer, but whether this involves Wnt signalling, a major oncogenic signalling pathway has not been studied. We aimed to determine the effect of iron loading on Wnt signalling using mutant APC (Caco-2 and SW480) and wild-type APC (HEK-293 and human primary fibroblasts) containing cell lines. Elevating cellular iron levels in Caco-2 and SW480 cells caused increased Wnt signalling as indicated by increased TOPFLASH reporter activity, increased mRNA expression of two known targets, c-myc and Nkd1, and increased cellular proliferation. In contrast wild-type APC and β-catenin-containing lines, HEK 293 and human primary fibroblasts were not responsive to iron loading. This was verified in SW480 cells that no longer induced iron-mediated Wnt signalling when transfected with wild-type APC. The cell line LS174T, wild type for APC but mutant for β-catenin, was also responsive suggesting that the role of iron is to regulate β-catenin. Furthermore, we show that E-cadherin status has no influence on iron-mediated Wnt signalling. We thus speculate that excess iron could exacerbate tumorigenesis in the background of APC loss, a common finding in cancers.Oncogene (2008) 27, 966–975; doi:10.1038/sj.onc.1210711; published online 13 August 2007 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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