Malignant Mesothelioma: Mechanism of Carcinogenesis
Résumé
Our present knowledge of the mechanism of mesothelial carcinogenesis results from pathophysiological and toxicological research carried out in vivo in rodents and in mammalian cells in culture and from biological and molecular studies of malignant mesothelioma (MM) tissue samples and cell lines from humans and experimental animals. In this latter context, most experimental studies have been based on the cellular and/or animal responses to asbestos fibers and in genetically modified mice. These investigations have provided a body of data on the cellular and molecular effects of asbestos fibers on mesothelial cells and the mesothelium, including genomic and genetic changes and alterations of regulatory and signaling pathways. Human MM has been characterized at the genomic, genetic, epigenetic, and physiological levels, with the development of large-scale analyses allowing global integration of the networks involved in the transformation of the mesothelial cell. The aim of the present work is to propose a potential mechanism of mesothelial carcinogenesis by integrating data based on cellular and molecular effects of asbestos fibers on mesothelial cells, with altered physiological and molecular features of malignant mesothelioma cells.
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