Umar S, Morris A P, Kourouma F, Sellin J H
Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Medical School, Houston, Texas, USA.
Cell Prolif. 2003 Dec;36(6):361-75. doi: 10.1046/j.1365-2184.2003.00291.x.
Diet plays an important role in promoting and/or preventing colon cancer; however, the effects of specific nutrients remain uncertain because of the difficulties in correlating epidemiological and basic observations. Transmissible murine colonic hyperplasia (TMCH) induced by Citrobacter rodentium, causes significant hyperproliferation and hyperplasia in the mouse distal colon and increases the risk of subsequent neoplasia. We have recently shown that TMCH is associated with an increased abundance of cellular beta-catenin and its nuclear translocation coupled with up-regulation of its downstream targets, c-myc and cyclin D1. In this study, we examined the effects of two putatively protective nutrients, calcium and soluble fibre pectin, on molecular events linked to proliferation in the colonic epithelium during TMCH. Dietary intervention incorporating changes in calcium [high (1.0%) and low (0.1%)] and alterations in fibre content (6% pectin and fibre-free) were compared with the standard AIN-93 diet (0.5% calcium, 5% cellulose), followed by histomorphometry and immunochemical assessment of potential oncogenes. Dietary interventions did not alter the time course of Citrobacter infection. Both 1.0% calcium and 6% pectin diet inhibited increases in proliferation and crypt length typically seen in TMCH. Neither the low calcium nor fibre-free diets had significant effect. Pectin diet blocked increases in cellular beta-catenin, cyclin D1 and c-myc levels associated with TMCH by 70%, whereas neither high nor low calcium diet had significant effect on these molecules. Diets supplemented with either calcium or pectin therefore, exert anti-proliferative effects in mouse distal colon involving different molecular pathways. TMCH is thus a diet-sensitive model for examining the effect of specific nutrients on molecular characteristics of the pre-neoplastic colonic epithelium.
饮食在促进和/或预防结肠癌方面起着重要作用；然而，由于难以将流行病学观察结果与基础研究结果相关联，特定营养素的作用仍不明确。鼠柠檬酸杆菌诱导的可传播性小鼠结肠增生（TMCH）会导致小鼠远端结肠显著的过度增殖和增生，并增加后续肿瘤形成的风险。我们最近发现，TMCH与细胞β-连环蛋白丰度增加及其核转位相关，同时其下游靶点c-myc和细胞周期蛋白D1上调。在本研究中，我们研究了两种被认为具有保护作用的营养素——钙和可溶性纤维果胶，对TMCH期间结肠上皮细胞增殖相关分子事件的影响。将改变钙含量（高钙1.0%和低钙0.1%）和纤维含量（6%果胶和无纤维）的饮食干预与标准AIN-93饮食（0.5%钙，5%纤维素）进行比较，随后通过组织形态计量学和潜在癌基因的免疫化学评估。饮食干预并未改变柠檬酸杆菌感染的时间进程。1.0%钙饮食和6%果胶饮食均抑制了TMCH中常见的增殖增加和隐窝长度增加。低钙饮食和无纤维饮食均无显著影响。果胶饮食使与TMCH相关的细胞β-连环蛋白、细胞周期蛋白D1和c-myc水平升高降低了70%，而高钙饮食和低钙饮食对这些分子均无显著影响。因此，补充钙或果胶的饮食对小鼠远端结肠具有抗增殖作用，涉及不同的分子途径。因此，TMCH是一种饮食敏感模型，用于研究特定营养素对癌前结肠上皮细胞分子特征的影响。
