TY - JOUR
T1 - SV40-dependent AKT activity drives mesothelial cell transformation after asbestos exposure
AU - Cacciotti, Paola
AU - Barbone, Dario
AU - Porta, Camillo
AU - Altomare, Deborah A.
AU - Testa, Joseph R.
AU - Mutti, Luciano
AU - Gaudino, Giovanni
PY - 2005/6/15
Y1 - 2005/6/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-05-0127
DO - 10.1158/0008-5472.CAN-05-0127
M3 - Article
C2 - 15958571
AN - SCOPUS:20444480256
VL - 65
SP - 5256
EP - 5262
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 12
ER -