Skip Navigation



Carcinogenesis Advance Access published online on April 13, 2007
Carcinogenesis, doi:10.1093/carcin/bgm090
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
28/9/2047    most recent
bgm090v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Aung, W.
Right arrow Articles by Saga, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aung, W.
Right arrow Articles by Saga, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Potential role of ferritin heavy chain in oxidative stress and apoptosis in human mesothelial and mesothelioma cells: implications for asbestos-induced oncogenesis

Winn Aung{dagger}, Sumitaka Hasegawa{dagger},*, Takako Furukawa and Tsuneo Saga

Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan

* Corresponding author: Sumitaka Hasegawa, MD. Ph.D., Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan, Tel: +81-43-206-3380, Fax: +81-43-206-0818, E-mail: shase{at}nirs.go.jp

Exposure to asbestos is a known etiological factor in malignant mesothelioma (MM). However, in vitro cell culture studies have provided paradoxical evidence that asbestos exposure to mesothelial cells causes cytotoxicity or apoptosis rather than malignant transformation. Although it has been shown that the iron associated with asbestos participates in the cell toxicity and likely MM pathogenesis via generation of reactive oxygen species (ROS), the molecular mechanism(s) largely remains unknown. Here we demonstrate that ferritin heavy chain (FHC), a core subunit of iron-binding protein ferritin, works as an anti-apoptotic protein against toxic asbestos and oxidative stress in human mesothelial cells and MM cells. We found that FHC was induced in asbestos-exposed MeT-5A human mesothelial cells. The mesothelial cell line stably expressing FHC generated less amount of hydrogen peroxide (H2O2), one of the main ROS, after asbestos exposure and was more resistant to apoptosis induced by H2O2 compared with the cells transfected with the empty vector. Next, we investigated biological roles of FHC in human MM cell. We found that NCI-H2052, a human MM cell line, had a higher expression of endogenous FHC than MeT-5A and used the cell to address FHC function in MM. NCI-H2052 showed reduced H2O2 production and an apoptosis resistant phenotype compared to MeT-5A. Suppression of the over-expressed FHC by using FHC siRNA rendered the MM cells sensitive to apoptosis, suggesting the contribution of FHC to apoptosis resistance of the MM cells. Our findings highlight the potential role of FHC in the pathogenesis of asbestos-induced mesothelioma.

{dagger} These authors contributed equally to this work.

Received January 4, 2007; revised February 28, 2007; accepted March 30, 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Neurosci.Home page
R. Sengupta, S. Burbassi, S. Shimizu, S. Cappello, R. B. Vallee, J. B. Rubin, and O. Meucci
Morphine Increases Brain Levels of Ferritin Heavy Chain Leading to Inhibition of CXCR4-Mediated Survival Signaling in Neurons
J. Neurosci., February 25, 2009; 29(8): 2534 - 2544.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.