SV40-dependent AKT activity drives mesothelial cell transformation after asbestos exposure

Paola Cacciotti, Dario Barbone, Camillo Porta, Deborah A. Altomare, Joseph R. Testa, Luciano Mutti, Giovanni Gaudino

Research output: Contribution to journalArticlepeer-review


Human malignant mesothelioma is an aggressive cancer generally associated with exposure to asbestos, although SV40 virus has been involved as a possible cofactor by a number of studies. Asbestos fibers induce cytotoxicity in human mesothelial cells (HMC), although cell survival activated by key signaling pathways may promote transformation. We and others previously reported that SV40 large T antigen induces autocrine loops in HMC and malignant mesothelioma cells, leading to activation of growth factor receptors. Now we show that SV40 induces cell survival via Akt activation in malignant mesothelioma and HMC cells exposed to asbestos. Consequently, prolonged exposure to asbestos fibers progressively induces transformation of SV40-positive HMC. As a model of SV40/asbestos cocarcinogenesis, we propose that malignant mesothelioma originates from a subpopulation of transformed stem cells and that Akt signaling is a novel therapeutic target to overcome malignant mesothelioma resistance to conventional therapies.

Original languageEnglish
Pages (from-to)5256-5262
Number of pages7
JournalCancer Research
Issue number12
Publication statusPublished - Jun 15 2005

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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