A possible novel src-related tyrosine kinase in cancer cells of LEC rats that develop hepatocellular carcinoma

Backgrounds/Aims: Src-related protein tyrosine kinase is known to be related to cell transformation. In this study, we report a possible novel src-related tyrosine kinase of 100 kDa specifically expressed in the nuclei of hepatocytes and/or cancer cells in Long-Evans Cinnamon rats, one of the experimental models of hepatocellular carcinoma. Methods: Src-related protein tyrosine kinase in hepatocytes of Long-Evans Cinnamon rats was analyzed by using immunohistochemistry and Western blot and in vitro tyrosine kinase assay using a specific antibody (src antibody) against a synthetic peptide corresponding to the conserved autophosphorylation site of src family tyrosine kinases. Results: Src-related protein was found to be expressed in the nuclei of hepatocytes and/or cancer cells in Long-Evans Cinnamon rat liver, exhibiting tyrosine kinase activity, and migrated to the position of 100 kDa. The protein quantity and activity of this 100-kDa src-related protein tyrosine kinase significantly increased with the progress of chronic hepatitis to hepatocellular carcinoma, especially in the tumorous portion of the liver. On the other hand, the 100-kDa src-protein tyrosine kinase was not observed in the nuclei of hepatocytes and/or cancer cells in normal age-matched control Wistar rats. Conclusions: Since the src-family tyrosine kinases have been observed at a molecular weight of 55 to 62 kDa and located in the hepatocellular membrane and/or cytoplasm, the 100-kDa src-related protein tyrosine kinase observed in the present study may be novel, and closely related to the pre-cancerous and cancerous process in Long-Evans Cinnamon rat liver.