Jain Swati S, AshokKumar Manickaraj, Bird Ranjana P
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
Tumour Biol. 2011 Oct;32(5):1005-12. doi: 10.1007/s13277-011-0202-5. Epub 2011 Jul 15.
Distal and proximal colon cancers have been recognized as two different disease types in human population. The environmental factors involved in the pathogenesis of the proximal and distal tumors also differ. The main objective of this study was to determine if obesity-augmented colonic tumors differ from each other if they are located in different regions of the colonic axis. Zucker obese rats were injected with azoxymethane (AOM) 10 mg/kg body weight/week for 2 weeks. The tumors appeared within 20 weeks. The highest proportion of the tumors was in the distal colon, and the number declined towards the splenic flexure. A number of proteins previously reported to be altered in tumor tissue were assessed in the present study in tumors appearing in proximal and distal regions. Distal colonic tumors had higher TNF-α R2, NF-κB, and IκBα levels than tumors of proximal origin. In contrast, IKKβ was decreased in the proximal tumors. Insulin receptor and insulin-like growth factor-1R were higher in distal tumors. The mitogen-activated protein kinase (ERK2) levels were similar in the tumor groups; however, the ERK1 was significantly higher in the distal tumor than in the proximal tumor. Our findings suggest that colon tumors induced by AOM in different colonic regions are different from each other with respect to differential expression of proteins and support the concept that these disease states could respond differently to tumor-promoting and inhibitory conditions. Moreover, these findings support the concept that cancer preventive or therapeutic agents need to be evaluated for their effectiveness on proximal as well as on distal tumors.
在人群中，近端结肠癌和远端结肠癌已被视为两种不同的疾病类型。近端和远端肿瘤发病机制中涉及的环境因素也有所不同。本研究的主要目的是确定，如果肥胖相关的结肠肿瘤位于结肠轴的不同区域，它们彼此是否存在差异。给肥胖的 Zucker 大鼠每周注射 10 mg/kg 体重的氧化偶氮甲烷（AOM），持续 2 周。肿瘤在 20 周内出现。肿瘤比例最高的是在远端结肠，数量向脾曲方向减少。在本研究中，对先前报道在肿瘤组织中发生改变的一些蛋白质，在近端和远端区域出现的肿瘤中进行了评估。远端结肠肿瘤的 TNF-α R2、NF-κB 和 IκBα 水平高于近端起源的肿瘤。相比之下，近端肿瘤中的 IKKβ 减少。胰岛素受体和胰岛素样生长因子 -1R 在远端肿瘤中更高。丝裂原活化蛋白激酶（ERK2）水平在肿瘤组中相似；然而，ERK1 在远端肿瘤中显著高于近端肿瘤。我们的研究结果表明，AOM 在不同结肠区域诱导的结肠肿瘤在蛋白质表达差异方面彼此不同，支持这些疾病状态可能对肿瘤促进和抑制条件有不同反应的概念。此外，这些发现支持这样的概念，即癌症预防或治疗药物需要评估其对近端和远端肿瘤的有效性。
