Liddle Forrester J, Frank David A
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Mol Carcinog. 2008 Feb;47(2):75-9. doi: 10.1002/mc.20371.
Recent studies have suggested the importance of interleukin (IL)-6 signaling in the development of colon cancer. Expression of IL-6 and the IL-6 receptor have been found to be elevated in colorectal carcinoma tissue, and IL-6 has been found to be critical for tumor formation in mouse models of colon cancer. IL-6 mediated activation of the transcription factor STAT1 has been shown to be important in protection of colorectal carcinoma cells from apoptotic signals. To test the hypothesis that the IL-6-STAT1 axis plays a role in early stages of colon cancer development, we examined the role of this pathway in the mouse multiple intestinal neoplasia (Min) model of intestinal tumorigenesis. Due to low fecundity, we were unable to generate Min mice lacking expression of IL-6. We then focused on the role of STAT1 in intestinal polyp formation in these animals. Min mice lacking STAT1 or heterozygous for STAT1 developed polyps in similar numbers as those expressing STAT1. Furthermore, the anatomic distribution and histological characteristics of these polyps did not vary among these populations. These results indicate that STAT1 does not play a role in the pathogenesis of the Min model for colon cancer. However, they do not rule out the possibility that STAT1 plays a role in other stages of colon cancer development.
近期研究表明白细胞介素（IL）-6信号传导在结肠癌发生发展过程中具有重要作用。已发现IL-6及其受体在结直肠癌组织中的表达升高，并且在结肠癌小鼠模型中，IL-6对肿瘤形成至关重要。IL-6介导的转录因子STAT1激活已被证明在保护结肠癌细胞免受凋亡信号影响方面具有重要作用。为了验证IL-6-STAT1轴在结肠癌发生早期阶段发挥作用这一假说，我们在肠道肿瘤发生的小鼠多发性肠肿瘤（Min）模型中研究了该信号通路的作用。由于繁殖力低，我们无法培育出缺乏IL-6表达的Min小鼠。随后，我们聚焦于STAT1在这些动物肠道息肉形成中的作用。缺乏STAT1的Min小鼠或STAT1杂合子小鼠形成息肉的数量与表达STAT1的小鼠相似。此外，这些息肉的解剖分布和组织学特征在这些群体中并无差异。这些结果表明STAT1在结肠癌Min模型的发病机制中不起作用。然而，它们并不排除STAT1在结肠癌发展的其他阶段发挥作用的可能性。
