Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 287, Issue 30, Pages 25292-25302Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.291195
Keywords
-
Categories
Funding
- National Science Council, Taiwan [NSC-99-2314-B-040-012-MY3]
- National Research Program for Genomic Medicine, National Science Council Grant [NSC-97-3112-B-001-016]
- National Science Council, Ministry of Education
- Chung Shan Medical University
Ask authors/readers for more resources
Epithelial-mesenchymal transition (EMT) is considered a critical event in the pathogenesis of lung fibrosis and tumor metastasis. During EMT, the expression of differentiation markers switches from cell-cell junction proteins such as E-cadherin to mesenchymal markers such as fibronectin. Although nickel-containing compounds have been shown to be associated with lung carcinogenesis, the role of nickel in the EMT process in bronchial epithelial cells is not clear. The aim of this study was to examine whether nickel contributes to EMT in human bronchial epithelial cells. We also attempted to clarify the mechanisms involved in NiCl2-induced EMT. Our results showed that NiCl2 induced EMT phenotype marker alterations such as up-regulation of fibronectin and down-regulation of E-cadherin. In addition, the potent antioxidant N-acetylcysteine blocked EMT and expression of HIF-1 alpha induced by NiCl2, whereas the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine restored the down-regulation of E-cadherin induced by NiCl2. Promoter hypermethylation of E-cadherin, determined by quantitative real time methyl-specific PCR and bisulfate sequencing, was also induced by NiCl2. These results shed new light on the contribution of NiCl2 to carcinogenesis. Specifically, NiCl2 induces down-regulation of E-cadherin by reactive oxygen species generation and promoter hypermethylation. This study demonstrates for the first time that nickel induces EMT in bronchial epithelial cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available