title: Long-term exposure of mesothelial cells to SV40 and asbestos leads to malignant transformation and chemotherapy resistance.
abstract: 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.
authors.affiliation: National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia 6009, Australia and.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Cleaver
authors.forename: Kasia
authors.initials: K
authors.lastname: Bhamidipaty
authors.forename: Ben
authors.initials: B
authors.lastname: Wylie
authors.forename: Theresa
authors.initials: T
authors.lastname: Connor
authors.forename: Cleo
authors.initials: C
authors.lastname: Robinson
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Robinson
authors.forename: Steven E
authors.initials: SE
authors.lastname: Mutsaers
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lake
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D003043:Cocarcinogenesis; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000952:Antigens, Polyomavirus Transforming; D012333:RNA, Messenger; D017638:Asbestos, Crocidolite