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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kroczynska, Barbara Vacek, Pamela Elmishad, Amira G. Mossman, Brooke T. Cutrone, Rochelle Pass, Harvey I. Bocchetta, Maurizio Yang, Haining Ramos-nino, Maria Carbone, Michele |
| Description | Author Affiliation: Kroczynska B ( Thoracic Oncology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA.); |
| Abstract | Only a fraction of subjects exposed to asbestos develop malignant mesothelioma (MM), suggesting that additional factors may render some individuals more susceptible. We tested the hypothesis that asbestos and Simian virus (SV40) are cocarcinogens. Asbestos and SV40 in combination had a costimulatory effect in inducing ERK1/2 phosphorylation and activator protein-1 (AP-1) activity in both primary Syrian hamster mesothelial cells (SHM) and primary human mesothelial cells (HM). Ap-1 activity caused the expression and activation of matrix metalloprotease (MMP)-1 and MMP-9, which in turn led to cell invasion. Experiments using siRNA and chemical inhibitors confirmed the specificity of these results. The same effects were observed in HM and SHM. Experiments in hamsters showed strong cocarcinogenesis between asbestos and SV40: SV40 did not cause MM, asbestos caused MM in 20% of hamsters, and asbestos and SV40 together caused MM in 90% of hamsters. Significantly lower amounts of asbestos were sufficient to cause MM in animals infected with SV40. Our results indicate that mineral fibers and viruses can be cocarcinogens and suggest that lower amounts of asbestos may be sufficient to cause MM in individuals infected with SV40. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 38 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Asbestos, Crocidolite Toxicity Carcinogens Epithelial Cells Metabolism Epithelium Gene Expression Regulation, Neoplastic Mesothelioma Simian Virus 40 Pathogenicity Animals Cells, Cultured Cricetinae Enzyme Activation Cytology Pathology Gene Expression Regulation, Enzymologic Matrix Metalloproteinase 1 Genetics Matrix Metalloproteinase 9 Mesocricetus Etiology Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Proto-Oncogene Proteins C-fos RNA, Small Interfering Repressor Proteins Transcription Factor AP-1 Transcriptional Activation Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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