权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

β-catenin gene mutations in rat inflammation-induced colon carcinogenesis model and the modification and influence on histopathological and morphological change of the neoplastic lesions

炎症诱导的大鼠结肠癌模型中β-catenin基因突变及其对肿瘤病变组织病理形态学变化的修饰及影响

基本信息

批准号：
11670210
负责人：
YOSHIMI Naoki
金额：
$ 2.05万
依托单位：
GIFU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Activating mutations in the β-catenin gene is thought to be responsible for the excessive β-catenin signaling involved in the majority of carcinogen-induced colonic carcinomas. To determine if β-catenin signaling is involved in the initial stage of colon carcinogenesis, mutational analysis of the gene and immunohistochemistry for β-catenin protein were performed in the early appearing lesions, including aberrant crypt foci (ACF), of colonic mucosa in rats given azoxymethane (AOM). Male F344 rats received s.c. injections of AOM at a dose of 15 mg/kg body weight, once weekly for 3 weeks and sacrificed 10 weeks after the carcinogen treatment. The colonic mucosa was examined in en face preparations and in serial sections after the observation in whole mount preparations. Microscopical observations in the cross sections have shown two populations of histologically altered crypts. The first type had a macroscopic feature resembling ACF (histologically altered crypts with ACF appearance ; HACA). The second type of altered crypts did not have the ACF-like appearance and could not be clearly distinguished from adjacent normal crypts in whole mount preparations (histologically altered crypts with macroscopically normal-like appearance ; HACN). The β-catenin gene mutations were recognized in 10 out of 15 HACN (67%) and 3 of 15 HACA (20%). Frequent immunoreactivity of β-catenin protein was seen in the cytoplasm of HACN (13 out of 15 cases), whereas apparent accumulation was not confirmed in any HACA analyzed. These results suggest that i) there are two types of putative preneoplastic lesions in cancer-predisposed colonic mucosa and β-catenin signaling may contribute to the initial stage of colon carcinogenesis, ii) HACN are more likely to be direct precursors of colon tumors than HACA in the rat colon carcinogenesis.

β-连环蛋白基因的激活突变被认为是导致大多数致癌物诱发的结肠癌中过度的 β-连环蛋白信号传导的原因。为了确定β-连环蛋白信号传导是否参与结肠癌发生的初始阶段，对给予氧化偶氮甲烷（AOM）的大鼠的结肠粘膜早期出现的病变（包括异常隐窝灶（ACF））进行了基因突变分析和β-连环蛋白免疫组织化学分析。雄性 F344 大鼠接受皮下注射。注射 AOM，剂量为 15 mg/kg 体重，每周一次，持续 3 周，并在致癌物治疗后 10 周处死。在整体标本中观察后，在正面标本中和连续切片中检查结肠粘膜。横截面的显微镜观察显示出两个组织学改变的隐窝群体。第一种类型具有类似于 ACF 的宏观特征（具有 ACF 外观的组织学改变的隐窝；HACA）。第二种类型的改变的隐窝不具有类似ACF的外观，并且在整个安装制剂中不能与相邻的正常隐窝清楚地区分开来（具有宏观正常外观的组织学改变的隐窝；HACN）。 β-连环蛋白基因突变在 15 个 HACN 中的 10 个（67%）和 15 个 HACA 中的 3 个（20%）中被识别。在 HACN 的细胞质中观察到频繁的 β-连环蛋白免疫反应性（15 例中的 13 例），而在任何 HACA 分析中均未证实明显的积累。这些结果表明，i）易患癌症的结肠粘膜中有两种推定的癌前病变，β-连环蛋白信号传导可能有助于结肠癌发生的初始阶段，ii）在大鼠结肠癌发生中，HACN 比 HACA 更有可能是结肠肿瘤的直接前体。