Long-term exposure of mesothelial cells to SV40 and asbestos leads to malignant transformation and chemotherapy resistance

Carcinogenesis. 2014 Feb;35(2):407-14. doi: 10.1093/carcin/bgt322. Epub 2013 Oct 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / toxicity*
  • Apoptosis / drug effects
  • Asbestos, Crocidolite / toxicity*
  • Blotting, Western
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Cells, Cultured
  • Cocarcinogenesis*
  • Drug Resistance, Neoplasm*
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mesothelioma / genetics
  • Mesothelioma / metabolism
  • Mesothelioma / pathology*
  • Mesothelioma, Malignant
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peritoneum / drug effects
  • Peritoneum / metabolism
  • Peritoneum / pathology
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction


  • Antigens, Polyomavirus Transforming
  • RNA, Messenger
  • Asbestos, Crocidolite