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β-catenin accumulation in nuclei of hepatocellular carcinoma cells up-regulates glutathione-s-transferase M3 mRNA 被引量:1

β-catenin accumulation in nuclei of hepatocellular carcinoma cells up-regulates glutathione-s-transferase M3 mRNA
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摘要 AIM: To identify the differentially over-expressed genes associated with β-catenin accumulation in nuclei of hepatocellular carcinoma (HCC) cells. METHODS: Differentially expressed genes were identified in radiation-induced B6C3 F1 mouse HCC cells by mRNA differential display, Northern blot and RT-PCR, respectively. Total glutathione-s-transferase (GST) activity was measured by GST activity assay and β-catenin localization was detected with immunostaining in radiation-induced mouse HCC cells and in HepG2 cell lines.RESULTS: Two up-regulated genes, glutamine synthetase and glutathione-s-transferase M3 (GSTM3), were identified in radiation-induced mouse HCC cells. Influence of β-catenin accumulation in nuclei of HCC cells on upregulation of GSTM3 mRNA was investigated. The nearby upstream domain of GSTM3 contained the β-catenin/TcfLef consensus binding site sequences [5'-(A/T)(A/T) CAAAG-3'], and the total GST activity ratio was considerably higher in B6C3F1 mouse HCC cells with β-catenin accumulation in nuclei of HCC cells than in those without β-catenin accumulation (0.353 ± 0.117vs 0.071 ± 0.064, P < 0.001). The TWS119 (a distinct GSK-3β inhibitor)-induced total GST activity was significantly higher in HepG2 cells with β-catenin accumulation than in those without β-catenin accumulation in nuclei of HCC cells. Additionally, the GSTM3 mRNA level was significantly higher at 24 h than at 12 h in TWS119-treated HepG2 cells. CONCLUSION: β-catenin accumulation increases GST activity in nuclei of HCC cells, and GSTM3 may be a novel target gene of the β-catenin/Tcf-Lef complex. AIM: To identify the differentially over-expressed genes associated with β-catenin accumulation in nuclei of hepatocellular carcinoma (HCC) cells. METHODS: Differentially expressed genes were identified in radiation-induced B6C3 F1 mouse HCC cells by mRNA differential display, Northern blot and RT-PCR, respectively. Total glutathione-s-transferase (GST) activity was measured by GST activity assay and β-catenin localization was detected with immunostaining in radiation-induced mouse HCC cells and in HepG2 cell lines.RESULTS: Two up-regulated genes, glutamine synthetase and glutathione-s-transferase M3 (GSTM3), were identified in radiation-induced mouse HCC cells. Influence of β-catenin accumulation in nuclei of HCC cells on upregulation of GSTM3 mRNA was investigated. The nearby upstream domain of GSTM3 contained the β-catenin/TcfLef consensus binding site sequences [5’-(A/T)(A/T) CAAAG-3’], and the total GST activity ratio was considerably higher in B6C3F1 mouse HCC cells with β-catenin accumulation in nuclei of HCC cells than in those without β-catenin accumulation (0.353 ± 0.117vs 0.071 ± 0.064, P 0.001). The TWS119 (a distinct GSK-3β inhibitor)-induced total GST activity was significantly higher in HepG2 cells with β-catenin accumulation than in those without β-catenin accumulation in nuclei of HCC cells. Additionally, the GSTM3 mRNA level was significantly higher at 24 h than at 12 h in TWS119-treated HepG2 cells. CONCLUSION: β-catenin accumulation increases GST activity in nuclei of HCC cells, and GSTM3 may be a novel target gene of the β-catenin/Tcf-Lef complex.
出处 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第13期1772-1778,共7页 世界胃肠病学杂志(英文版)
基金 Supported by National Natural Science Foundation of China,81070887 Scientific Research Foundation for the ReturnedOverseas Chinese Scholars State Education Ministry to TangHB Grants from South-Central University for Nationalities,No. XTZ10001, No. XTZ09001, and No. YZZ09007,China
关键词 β-catenin accumulation Differential display analysis Glutathione-s-transferase M3 Hepatocellular carcinoma RADIATION 差异表达基因 肝癌细胞 谷胱甘肽 细胞核 转移酶 积累 HepG2细胞 mRNA差异显示
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