β-catenin accumulation in nuclei of hepatocellular carcinoma cells up-regulates glutathione-s-transferase M3 mRNA.

Abstract:

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 up-regulation of GSTM3 mRNA was investigated. The nearby upstream domain of GSTM3 contained the β-catenin/Tcf-Lef 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 ± 0.117 vs. 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.

journal_name

World J Gastroenterol

authors

Li YS,Liu M,Nakata Y,Tang HB

doi

10.3748/wjg.v17.i13.1772

subject

Has Abstract

pub_date

2011-04-07 00:00:00

pages

1772-8

issue

13

eissn

1007-9327

issn

2219-2840

journal_volume

17

pub_type

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