目的探讨脱氧胆酸(DOC)对肠道息肉恶变的影响及可能的分子机制。方法将24只4周龄Apcmin/+小鼠(该小鼠可自发形成肠道腺瘤)随机分为对照组(常规饮用水)及DOC组(含0.2%DOC饮用水),12周后处死,观察各组小鼠肠道息肉数目、大小及分布。HE染...目的探讨脱氧胆酸(DOC)对肠道息肉恶变的影响及可能的分子机制。方法将24只4周龄Apcmin/+小鼠(该小鼠可自发形成肠道腺瘤)随机分为对照组(常规饮用水)及DOC组(含0.2%DOC饮用水),12周后处死,观察各组小鼠肠道息肉数目、大小及分布。HE染色评价息肉病理类型,免疫组织化学染色法检测细胞增殖标记物(proliferating cell nuclear antigen,PCNA)及Wnt通路关键分子β-catenin和cyclin D1的表达。结果 DOC组肠道息肉总数较对照组增加165%(57.00±3.07 vs 21.50±4.69,P<0.001),其中小肠中段和远段的息肉数量分别增加了153%和371%。DOC组小肠息肉大、中、小直径(>2 mm、1~2 mm和<1mm)息肉数量与对照组对比分别增加89%(10.38±4.41 vs 5.50±2.93,P<0.05)、295%(30.62±7.73 vs 7.75±4.59,P<0.001)和112%(13.50±5.78 vs 6.38±2.45,P<0.01)。HE染色示DOC组75%远段小肠和近段结肠发生黏膜内癌,余25%为中-高级别上皮内瘤变,而对照组仅为腺瘤未见癌变。免疫组织化学染色示DOC组PCNA阳性细胞数较对照组增加81%(90.83±2.60 vs50.10±4.51,P<0.001),β-catenin由胞膜向胞质和胞核移位,cyclin D1胞核内表达增加(β-catenin:87.75±4.35 vs 56.30±4.29,P<0.001;cyclin D1:71.93±4.01 vs 35.40±3.02,P<0.001)。结论 DOC可能通过干预Wnt通路促进Apcmin/+小鼠肠道息肉细胞增殖,促使肠道腺瘤发展成为肠癌。展开更多
AIM:To investigate whether Recql5,a DNA helicase that plays an important role in the maintenance of genome integrity,is a tumor suppressor in the gastrointestinal tract in mice.METHODS:We generated cohorts of both Rec...AIM:To investigate whether Recql5,a DNA helicase that plays an important role in the maintenance of genome integrity,is a tumor suppressor in the gastrointestinal tract in mice.METHODS:We generated cohorts of both Recql5-proficient and Recql5-deficient Apcmin/+mice and compared the tumor susceptibility in their gastrointestinal tracts.RESULTS:Recql5 deficiency in Apcmin/+mice resulted in a significant increase in the tumor incidence in both the colon(P=0.0162)and the small intestine(P<0.01).These findings have provided the first genetic evidence for a tumor suppression role of Recql5 in the gastrointestinal tract of mice.Importantly,since mouse Recql5 and human RECQL5 are highly conserved,these findings also suggest that RECQL5 may be a tu-mor suppressor for human colon cancer.CONCLUSION:Recql5 has a tumor suppression role in the mouse gastrointestinal tract.展开更多
文摘目的探讨脱氧胆酸(DOC)对肠道息肉恶变的影响及可能的分子机制。方法将24只4周龄Apcmin/+小鼠(该小鼠可自发形成肠道腺瘤)随机分为对照组(常规饮用水)及DOC组(含0.2%DOC饮用水),12周后处死,观察各组小鼠肠道息肉数目、大小及分布。HE染色评价息肉病理类型,免疫组织化学染色法检测细胞增殖标记物(proliferating cell nuclear antigen,PCNA)及Wnt通路关键分子β-catenin和cyclin D1的表达。结果 DOC组肠道息肉总数较对照组增加165%(57.00±3.07 vs 21.50±4.69,P<0.001),其中小肠中段和远段的息肉数量分别增加了153%和371%。DOC组小肠息肉大、中、小直径(>2 mm、1~2 mm和<1mm)息肉数量与对照组对比分别增加89%(10.38±4.41 vs 5.50±2.93,P<0.05)、295%(30.62±7.73 vs 7.75±4.59,P<0.001)和112%(13.50±5.78 vs 6.38±2.45,P<0.01)。HE染色示DOC组75%远段小肠和近段结肠发生黏膜内癌,余25%为中-高级别上皮内瘤变,而对照组仅为腺瘤未见癌变。免疫组织化学染色示DOC组PCNA阳性细胞数较对照组增加81%(90.83±2.60 vs50.10±4.51,P<0.001),β-catenin由胞膜向胞质和胞核移位,cyclin D1胞核内表达增加(β-catenin:87.75±4.35 vs 56.30±4.29,P<0.001;cyclin D1:71.93±4.01 vs 35.40±3.02,P<0.001)。结论 DOC可能通过干预Wnt通路促进Apcmin/+小鼠肠道息肉细胞增殖,促使肠道腺瘤发展成为肠癌。
基金Supported by Grants RO1 CA88939,P20 CA103736 from the US National Institutes of HealthSearle Scholar Award 01-E-109 from the Searle Scholar Program
文摘AIM:To investigate whether Recql5,a DNA helicase that plays an important role in the maintenance of genome integrity,is a tumor suppressor in the gastrointestinal tract in mice.METHODS:We generated cohorts of both Recql5-proficient and Recql5-deficient Apcmin/+mice and compared the tumor susceptibility in their gastrointestinal tracts.RESULTS:Recql5 deficiency in Apcmin/+mice resulted in a significant increase in the tumor incidence in both the colon(P=0.0162)and the small intestine(P<0.01).These findings have provided the first genetic evidence for a tumor suppression role of Recql5 in the gastrointestinal tract of mice.Importantly,since mouse Recql5 and human RECQL5 are highly conserved,these findings also suggest that RECQL5 may be a tu-mor suppressor for human colon cancer.CONCLUSION:Recql5 has a tumor suppression role in the mouse gastrointestinal tract.
