Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human: a study of histopathology, B-catenin and p53 expression and the role of inflammation
Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human: a study of histopathology, B-catenin and p53 expression and the role of inflammation
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DOI：
10.1093/carcin/21.4.757
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发表时间：
2000-04-01
期刊：
影响因子：
4.7
通讯作者：
Flanigan, A
中科院分区：
文献类型：
--
作者：
Cooper, HS;Murthy, S;Flanigan, A
结肠炎的动物模型，发展发育不良和癌症类似于人类溃疡性结肠炎，需要进一步研究发育不良癌症序列。本研究描述了B-连环蛋白和p53沿着的表达以及组织病理学和炎症评分，因为它们与葡聚糖硫酸钠（DSS）结肠炎模型中的异型增生和癌症有关。Swiss韦伯斯特小鼠仅用5%DSS喂养如下：A组，4个DSS周期，总共84天（1个周期= 7天DSS + 14天H2O）：B组，4个周期DSS +120天H2O，共204天，C组，7天DSS +180天H2O，共187天; D组，DSS 7天，H_2O 90天，共97天，A-D组异型增生和/或癌的发生率分别为15.8%、37.5%、18.1%和0%。如在人类中观察到的，异型增生和/或癌症以扁平病变或异型增生相关病变或肿块（DALM）的形式发生。33%的癌症具有相关异型增生。在A组内，与没有异型增生和/或癌症的动物相比，具有异型增生和/或癌症的动物的炎症评分显著更高（P < 0.05-P < 0.0001），炎症评分在具有癌症的动物中显著高于具有异型增生的动物（P < 0.015），并且在平坦异型增生和/或癌症中显著高于DALM（P < 0.0042）。在100%的DALM和5.8%的Bat异型增生和/或癌症中，B-连环蛋白显示出从细胞膜到细胞质和/或细胞核的易位。94.2%的扁平型异型增生和/或癌组织仅有细胞膜表达，而DALM组织仅有细胞膜表达（P < 0.0001）。只有7.4%的发育异常和/或癌症显示p53的核表达。在DSS模型中的结肠炎相关的发育异常和/或癌症中：（1）组织学类似于人中的组织学;（ii）炎症在发育异常癌症序列中起重要作用，并且发育异常和/或癌症是否生长为Bat病变或DALM;（iii）Bat异型增生和/或癌症与DALM的早期分子途径不同，其中B-连环蛋白的核/胞质易位是DALM中的早期事件，而不是扁平异型增生和/或癌症;和（iv）p53在发育异常和/或癌症中作用很小或没有作用。该模型为研究炎症的作用、分子事件和化学预防剂在结肠炎相关肿瘤中的作用提供了极好的载体。
Animal models of colitis, which develop dysplasia and cancer similar to human ulcerative colitis are needed to further investigate the dysplasia cancer sequence. This study describes the expression of B-catenin and p53 along with the histopathology and inflammation scores as they relate to dysplasia and cancer in the dextran sulfate sodium (DSS) colitis model. swiss Webster mice mere fed with 5% DSS as follows: group A, four cycles of DSS, 84 days total (1 cycle = 7 days DSS + 14 days H2O); group B, four cycles DSS followed by 120 days H2O, 204 days total; group C, 7 days DSS followed by 180 days H2O, 187 days total; group D, 7 days DSS followed by 90 days H2O, 97 days total, The incidences of dysplasia and/or cancer mere 15.8, 37.5, 18.1 and 0% in groups A-D, respectively. Dysplasia and/or cancer occurred as flat lesions or as dysplasia-associated lesion or mass (DALM) as observed in the human, Thirty-three percent of cancers had associated dysplasia, Within group A, inflammation scores were significantly higher in animals with dysplasia and/or cancer compared with those without dysplasia and/or cancer (P < 0.05-P < 0.0001), Inflammation scores were significantly higher in animals with cancers versus those with dysplasia (P < 0.015) and in flat dysplasia and/or cancer versus DALM (P < 0.0042). B-catenin showed translocation from the cell membrane to the cytoplasm and/or nucleus in 100% of DALM and 5.8% of Bat dysplasia and/or cancer. A total of 94.2% of flat dysplasia and/or cancer had exclusive cell membrane expression compared with 0% DALM (P < 0.0001). Only 7.4% of dysplasia and/ or cancer showed nuclear expression of p53, In colitis-associated dysplasia and/or cancer in the DSS model: (1) histology resembles that in the human; (ii) inflammation plays a significant role in the dysplasia cancer sequence and whether dysplasia and/or cancer grows as a Bat lesion or a DALM; (iii) the early molecular pathways are different for Bat dysplasia and/or cancer versus DALM, with nuclear/ cytoplasmic translocation of B-catenin as an early event in DALM but not flat dysplasia and/or cancer; and (iv) p53 has little or no role in dysplasia and/or cancer. This well characterized model provides an excellent vehicle for studying the roles of inflammation, the molecular events and the role of chemopreventive agents in colitis-associated neoplasia.