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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer
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Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer

机译：Paneth细胞标志物在肠绒毛和结肠隐窝中的表达表征了饮食诱发的小鼠散发性肠癌风险

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摘要

Nutritional and genetic risk factors for intestinal tumors are additive on mouse tumor phenotype, establishing that diet and genetic factors impact risk by distinct combinatorial mechanisms. In a mouse model of dietary-induced sporadic small and large intestinal cancer in WT mice in which tumor etiology, lag, incidence, and frequency reflect >90% of intestinal cancer in Western societies, dietary-induced risk altered gene expression profiles predominantly in villus cells of the histologically normal mucosa, in contrast to targeting of crypt cells by inheritance of an Apc~(1638N) allele or homozygous inactivation of p21~(Waf1/cip1), and profiles induced by each risk factor were distinct at the gene or functional group level. The dietary-induced changes in villus cells encompassed ectopic expression of Paneth cell markers (a lineage normally confined to the bottom of small intestinal crypts), elevated expression of the Wnt receptor Fzd5 and of EphB2 (genes necessary for Paneth cell differentiation and localization to the crypt bottom), and increased Wnt signaling in villus cells. Ectopic elevation of these markers was also present in the colon crypts, which are also sites of sporadic tumors in the nutritional model. Elevating dietary vitamin D_3 and calcium, which prevents tumor development, abrogated these changes in the villus and colon cells. Thus, common intestinal cancer driven by diet involves mechanisms of tumor development distinct from those mechanisms that cause tumors induced by the rare inheritance of a mutant adenomatous polyposis coli (Apc) allele. This is fundamental for understanding how common sporadic tumors arise and in evaluating relative risk in the population.
机译：肠道肿瘤的营养和遗传风险因素与小鼠肿瘤表型相加，从而证明饮食和遗传因素通过独特的组合机制影响风险。在WT小鼠的饮食引起的散发性小肠和大肠癌的小鼠模型中，肿瘤病因，滞后，发病率和发生频率反映了西方社会> 90％的肠癌，饮食引起的风险主要是在绒毛中改变了基因表达谱在组织学上正常的粘膜细胞中，与通过Apc〜（1638N）等位基因的遗传或p21〜（Waf1 / cip1）的纯合失活对隐窝细胞的靶向形成鲜明对照，并且由每种危险因素诱导的谱在基因或功能上均不同组级别。饮食引起的绒毛细胞变化包括Paneth细胞标志物的异位表达（谱系通常局限于小肠隐窝的底部），Wnt受体Fzd5和EphB2的表达升高（Paneth细胞分化和定位于该细胞所需的基因）。隐窝底部），并增加绒毛细胞中的Wnt信号传导。这些标记的异位升高也出现在结肠隐窝中，在营养模型中，它们也是散发性肿瘤的部位。增加饮食中的维生素D_3和钙可防止肿瘤的发展，可消除绒毛和结肠细胞中的这些变化。因此，饮食驱动的普通肠癌涉及肿瘤发展的机制，不同于引起突变性腺瘤性息肉病大肠杆菌（Apc）等位基因罕见遗传诱导的肿瘤的机制。这对于理解常见的散发性肿瘤如何产生以及评估人群的相对危险性至关重要。

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  • 作者

    Donghai Wang; Karina Peregrina; Elena Dhima; Elaine Y. Lin; John M. Mariadason; Leonard H. Augenlicht;

  • 作者单位

    Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467,Department of Hematology, Peking University First Hospital, Beijing 100034, China;

    Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467;

    Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467;

    Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467;

    Ludwig Institute for Cancer Research,Austin Hospital, Melbourne, Heidelberg, Victoria 3084, Australia;

    Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    sporadic; colon cancer; western diet; microarray;

    机译：零星的结肠癌;西餐微阵列;

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