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-kappaB 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.