Oncogenes signal transduction factors expressed

The tumor-promoting activity of OA class compounds is dne to their inhibitory activity of protein phosphatases, which increases phosphorylation/activation of varions proteins involved in the signal transduction pathways regulating the cell cycle and cell transformation. ° Different effects of OA leading to transformation of cells were reported, such as induction of mitosis, ° ° cycle progression, " as well as cell proliferation genes and proto-oncogenes expression. " It has been demonstrated that OA induces the release and expression of tumor necrosis factor-a (TNF-a) and other cytokines, phosphorylation of the tnmor snppressors p53 and retinoblastoma pRb proteins, and activation and induction of the nnclear transcription factors, such as activator protein-1 (AP-1) andNF-KB. ... 

Mineral fibers, particularly asbestos, can activate protein kinase C and increase expression of ornithine decarboxylase, the proto-oncogenes, c-fos, and c-jun (18-20), and the nuclear transcription factor, NF-kB (21). All these events are associated with cell proliferation and, potentially, with neoplastic transformation. Recently, Zanella et al. (22) have shown that asbestos activates the mitosis-associated kinase (MAP) system, apparently through interaction with the epidermal growth factor receptor, probably implying that some of these events are mediated by signal transduction pathways that start on the cell surface, rather than by fiber uptake, although this point needs to be directly examined. 

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