Abnormal differentiation of tumor cells and tyrosine kinase regulation

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Inflammatory cells are involved in tumor growth and development through various inflammatory mediators. Inflammatory cytokines activate the NF-kB and JAK/STAT pathways. We have investigated the function of SOCS family and Spred family proteins which regulate cytokine signaling, on tumorigenesi. In model mice lacking SOCS1 or SOCS3 genes, we found that carcinogen-induced tumorigensis was promoted. In human hepatocellular carcinoma, SOCS1 and SOCS3 gene expression was silenced. We also found that human SPRED1 is responsible for neurofibromatosis type I like disease.