mRNA expression patterns in different stages of asbestos-induced carcinogenesis in rats

Human malignant mesotheliomas are induced almost exclusively by fibrous dus ts. The nature of interactions between fibers and target cells, and the mol ecular mechanisms leading to tumorigenesis, are not Set understood. Here, t he mRNA expression patterns at different stages of asbestos-induced carcino genesis in rats were monitored by suppression subtractive hybridization (SS H) and array assay. Several genes mere upregulated in pretumorous tissues f rom asbestos-treated rats, in asbestos-induced tumors and in cells treated with asbestos ill vitro. The upregulation of the proto-oncogene c-myc, fra- 1 and egfr in fiber-induced carcinogenesis was demonstrated at different st ages of carcinogenesis. A possible role of Fra-1 as one of the dimeric prot eins generating the AP-1 transcription factor was substantiated by its dose -dependent expression in mesothelial cells treated with asbestos lit vitro, The upregulation of osteopontin (an extracellular matrix protein) and of z yxin and integrin-linked kinase (intracellular proteins associated with the focal adhesion contact), indicate that fibers may affect integrin-linked s ignal transduction and extracellular matrix proteins.