SV40-induced expression of calretinin protects mesothelial cells from asbestos cytotoxicity and may be a key factor contributing to mesothelioma pathogenesis.

Détails

ID Serval
serval:BIB_64610885AF14
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
SV40-induced expression of calretinin protects mesothelial cells from asbestos cytotoxicity and may be a key factor contributing to mesothelioma pathogenesis.
Périodique
American Journal of Pathology
Auteur(s)
Henzi T., Blum W.V., Pfefferli M., Kawecki T.J., Salicio V., Schwaller B.
ISSN
0002-9440
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
174
Numéro
6
Pages
2324-2336
Langue
anglais
Résumé
The calcium-binding protein calretinin has emerged as a useful marker for the identification of mesotheliomas of the epithelioid and mixed types, but its putative role in tumor development has not been addressed previously. Although exposure to asbestos fibers is considered the main cause of mesothelioma, undoubtedly, not all mesothelioma patients have a history of asbestos exposure. The question as to whether the SV40 virus is involved as a possible co-factor is still highly debated. Here we show that increased expression of SV40 early gene products in the mesothelial cell line MeT-5A induces the expression of calretinin and that elevated calretinin levels strongly correlate with increased resistance to asbestos cytotoxicity. Calretinin alone mediates a significant part of this protective effect because cells stably transfected with calretinin cDNA were clearly more resistant to the toxic effects of crocidolite than mock-transfected control cells. Down-regulation of calretinin by antisense methods restored the sensitivity to asbestos toxicity to a large degree. The protective effect observed in clones with higher calretinin expression levels could be eliminated by phosphatidylinositol 3-kinase (PI3K) inhibitors, implying an important role for the PI3K/AKT signaling (survival) pathway in mediating the protective effect. Up-regulation of calretinin, resulting from either asbestos exposure or SV40 oncoproteins, may be a common denominator that leads to increased resistance to asbestos cytotoxicity and thereby contributes to mesothelioma carcinogenesis.
Mots-clé
1-Phosphatidylinositol 3-Kinase/metabolism, Antigens, Polyomavirus Transforming, Asbestos, Crocidolite/adverse effects, Blotting, Western, Calcium-Binding Protein, Vitamin D-Dependent/metabolism, Cell Line, Tumor, Cell Transformation, Neoplastic/chemically induced, Cell Transformation, Neoplastic/metabolism, Gene Expression, Humans, Immunohistochemistry, Mesothelioma/chemically induced, Mesothelioma/virology, Polyomavirus Infections/complications, Polyomavirus Infections/metabolism, Proto-Oncogene Proteins c-akt/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction/physiology, Simian virus 40, Transfection, Tumor Virus Infections/complications, Tumor Virus Infections/metabolism, Up-Regulation
Pubmed
Web of science
Création de la notice
08/10/2009 11:34
Dernière modification de la notice
20/08/2019 15:20
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