Open AccessLong-term exposure of mesothelial cells to SV40 and asbestos leads to malignant transformation and chemotherapy resistance
Author(s) -
Amanda L. Cleaver,
Kasia Bhamidipaty,
Ben Wylie,
Theresa Connor,
Cleo Robinson,
B. W. Robinson,
Steven E. Mutsaers,
Richard Lake
Publication year - 2013
Publication title -
carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.688
H-Index - 204
eISSN - 1460-2180
pISSN - 0143-3334
DOI - 10.1093/carcin/bgt322
Subject(s) - asbestos , malignant transformation , chemotherapy , transformation (genetics) , mesothelial cell , cancer research , mesothelioma , medicine , term (time) , pathology , biology , materials science , genetics , gene , metallurgy , physics , quantum mechanics
Simian virus 40 (SV40) has been implicated in the development of several cancers including malignant mesothelioma. A definitive role for the virus in human mesothelioma has not been unequivocally demonstrated but has been rigorously debated. The virus clearly has oncogenic potential: the TAg is one of the most potent transforming proteins known and acts synergistically with crocidolite asbestos to transform mesothelial cells. In this study, we show that SV40 oncogenes alone can cause malignant transformation and that asbestos-induced DNA damage and apoptosis occurs principally in cycling cells. After long-term exposure (up to 100 days) to both SV40 and asbestos, cells become resistant to stress-induced senescence. Significantly, these cells demonstrate resistance to chemotherapy-induced apoptosis. This finding has implications for the development of effective treatment options for patients with mesothelioma.