Background. Specific mutations in the cationic trypsinogen gene (PRSS1) are disease causing in patients with hereditary pancreatitis, but the genetic background still remains mysterious in about 40%of patients with th...Background. Specific mutations in the cationic trypsinogen gene (PRSS1) are disease causing in patients with hereditary pancreatitis, but the genetic background still remains mysterious in about 40%of patients with the disease. It has been suggested that oxidative stress contributes to pancreatic damage. The glutathione s transferases (GSTs) represent major detoxification enzymes that protect cells from oxidative stress. Methods. In the present study we tested whether mutations in the MGST1 and GSTM3 genes or common deletions in the GSTT1 and GSTM1 genes are associated with hereditary pancreatitis. We analyzed the entire coding region of MGST1 and GSTM3 in 30 patients that were tested negative for PRSS1 mutations, and we studied 55 controls. For GSTT1 and GSTM1, we investigated 75 hereditary pancreatitis patients who had been tested negative for PRSS1 mutations, 135 hereditary pancreatitis patients with a PRSS1 mutation, and 183 controls. Patients were further subclassified with regard to age of onset of disease as a marker of severity. Results. No mutation was found in the MGST1 gene. In We GSTM3 gene, we detected a homozygous 670G > A polymorphism (V224I) with similar frequencies in patients and controls. We found no difference in the frequencies of the GSTT1 and GSTM1 null genotypes between patients and controls, and we detected no differences in age of onset in patients with or without GSTT1 and GSTM1 deletions. Conclusions. We conclude that genetic alterations in the MGST1, GSTM3, GSTT1, and GSTM1 genes do not play a dominant role in hereditary pancreatitis.展开更多
目的探讨微粒体谷胱甘肽S转移酶1(MGST1)在肝癌中的表达及其在肝癌细胞增殖、迁移和裸鼠成瘤中的作用。方法 Western blot检测人肝癌样品及肝癌细胞系中MGST1的表达;用慢病毒PLL3.7载体系统构建敲低MGST1的MHCC97H和HCCLM3细胞株及慢病...目的探讨微粒体谷胱甘肽S转移酶1(MGST1)在肝癌中的表达及其在肝癌细胞增殖、迁移和裸鼠成瘤中的作用。方法 Western blot检测人肝癌样品及肝癌细胞系中MGST1的表达;用慢病毒PLL3.7载体系统构建敲低MGST1的MHCC97H和HCCLM3细胞株及慢病毒p CDH载体系统构建过表达MGST1的SK-Hep-1细胞株后,用克隆形成实验检测细胞增殖能力;用Transwell实验检测细胞迁移能力;用皮下移植瘤实验检测MHCC97H细胞裸鼠成瘤能力。结果 71%(17/24)的肝癌组织中MGST1蛋白表达上调。敲低MGST1抑制MHCC97H和HCCLM3细胞的增殖、迁移能力(P<0.05);过表达MGST1促进SK-Hep-1细胞增殖、迁移(P<0.05);敲低MGST1的MHCC97H细胞裸鼠成瘤时间滞后(P<0.01),肿瘤体积减小(P<0.001),裸鼠生存期延长(P<0.001)。结论 MGST1过度表达促进肝癌发生发展,是治疗肝癌的一个新靶点。展开更多
文摘Background. Specific mutations in the cationic trypsinogen gene (PRSS1) are disease causing in patients with hereditary pancreatitis, but the genetic background still remains mysterious in about 40%of patients with the disease. It has been suggested that oxidative stress contributes to pancreatic damage. The glutathione s transferases (GSTs) represent major detoxification enzymes that protect cells from oxidative stress. Methods. In the present study we tested whether mutations in the MGST1 and GSTM3 genes or common deletions in the GSTT1 and GSTM1 genes are associated with hereditary pancreatitis. We analyzed the entire coding region of MGST1 and GSTM3 in 30 patients that were tested negative for PRSS1 mutations, and we studied 55 controls. For GSTT1 and GSTM1, we investigated 75 hereditary pancreatitis patients who had been tested negative for PRSS1 mutations, 135 hereditary pancreatitis patients with a PRSS1 mutation, and 183 controls. Patients were further subclassified with regard to age of onset of disease as a marker of severity. Results. No mutation was found in the MGST1 gene. In We GSTM3 gene, we detected a homozygous 670G > A polymorphism (V224I) with similar frequencies in patients and controls. We found no difference in the frequencies of the GSTT1 and GSTM1 null genotypes between patients and controls, and we detected no differences in age of onset in patients with or without GSTT1 and GSTM1 deletions. Conclusions. We conclude that genetic alterations in the MGST1, GSTM3, GSTT1, and GSTM1 genes do not play a dominant role in hereditary pancreatitis.
