The last two authors equally contributed to this work.
Erionite and asbestos differently cause transformation of human mesothelial cells
Version of Record online: 12 MAR 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 1, pages 12–20, 1 July 2007
How to Cite
Bertino, P., Marconi, A., Palumbo, L., Bruni, B. M., Barbone, D., Germano, S., Dogan, A.U., Tassi, G. F., Porta, C., Mutti, L. and Gaudino, G. (2007), Erionite and asbestos differently cause transformation of human mesothelial cells. Int. J. Cancer, 121: 12–20. doi: 10.1002/ijc.22687
- Issue online: 24 APR 2007
- Version of Record online: 12 MAR 2007
- Manuscript Accepted: 2 FEB 2007
- Manuscript Received: 8 JUN 2006
- AIRC (Associazione Italiana per la Ricerca sul Cancro)
- MARF (Mesothelioma Applied Research Foundation)
- Buzzi Unicem Foundation for mesothelioma research
- cell trans-formation
Malignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperation between asbestos and other cofactors, such as SV40 virus infection. Nevertheless, several cases of MM were associated with environmental exposure to erionite in Turkey, where SV40 was never isolated in MM specimens. We show here that erionite is poorly cytotoxic, induces proliferating signals and high growth rate in human mesothelial cells (HMC). Long term exposure to erionite, but not to asbestos fibers, transforms HMC in vitro, regardless of the presence of SV40 sequences, leading to foci formation in cultured monolayers. Cells derived from foci display constitutive activation of Akt, NF-κB and Erk1/2, show prolonged survival and a deregulated cell cycle, involving cyclin D1 and E overexpression. Our results reveal that erionite is able per se to turn HMC into transformed highly proliferating cells and disclose the carcinogenic properties of erionite, prompting for a careful evaluation of environmental exposure to these fibers. The genetic predisposition to the effect of erionite is a separate subject for investigation. © 2007 Wiley-Liss, Inc.