Objective:To investigate the mechanism responsible for lost sensibility of tyrosine aminotransferase (TAT) to dexamethasone(Dex) in human hepatoma cell line SMMC-7721 through examining the cDNA sequence of TAT and the status of glucocorticoid receptor (GR) pathway. Methods: The TAT cDNA fragment containing the full length of coding sequence was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and was sequenced.The expression of TAT mRNA was determined by real-time quantitative PCR to observe the influence of Dex on expression of TAT mRNA in SMMC-7721 cells.The experiement with HepG2 cells was performed as the control.Reporter genes (GRE-tk-LUC and GRE-MMTV-CAT) were transiently transfected into SMMC-7721 cells by electroporation.The induction efficiencies of LUC and CAT genes expression by Dex were examined and compared between SMMC-7721 cells and HepG2 cells.Results: The results showed that there was a same-sense mutation (Gln576Gln) in TAT cDNA sequence.TAT mRNA could be induced by Dex,with the maximal induction level being 2.22-folds in SMMC-7721 cells,which was significantly lower than that in HepG2 cells (15.1-fold increase,P＜0.01).Dex induced the expression of LUC and CAT genes in SMMC-7721 cells as well as the HepG2 cells.Conclusion: The induction efficiency of Dex for expression of TAT mRNA is decreased in SMMC-7721 cells,which might be due to the unchanged activity of TAT.