50%以上的大肠癌源于腺瘤性息肉，其恶性转变是遗传背景和环境因素共同作用的结果。本课题组前期应用APC min/+小鼠验证了EGFR和Wnt信号通路失调在FAP的息肉形成中起着重要作用，而脱氧胆酸（DOC）刺激可以加速“腺瘤-癌”这一恶性转变过程。本申请人已发表的成果证实Reg IV在小鼠大肠特异性的高表达，提示在这些部位的病变中可能扮演了重要角色，而我们预实验的结果发现DOC刺激使APC min/+小鼠肠道息肉组织Reg IV表达水平升高，而Reg IV属于胰腺再生蛋白，新近报道其通过调控EGFR和Wnt信号通路可以促进细胞增殖和拮抗凋亡，但对肠道息肉恶变的作用和机制仍不明确。因此本研究将首次探讨Reg IV在DOC促进APC min/+小鼠息肉恶变中的作用，其对IMCE细胞增殖和凋亡能力及EGFR和Wnt信号通路的影响，旨在为以Reg IV为靶点的大肠癌早期防治奠定实验基础。

It is said that 50% of colorectal cancer arising from adenomatous polyps, whereas the carcinogenesis is dependent of genetic background as well as environmental factors. We have previously confirmed that dysregulation of EGFR and Wnt signaling pathways played a pivotal role in the formation of polyps in an APCmin/+ mice. Additionally, DOC can accelerate the “adenoma-carcinoma” sequence by promoting the cell proliferation and inhibiting the apoptosis. Reg IV, a member of regenerating islet-derived protein, can also act as a trophic factor by the activation of EGFR and Wnt signaling pathways. I have published one paper identifying the expression level of Reg IV was upmost in the intestine in mice, suggesting the critical role of Reg IV in the pathogenesis of colorectal diseases. On the other hand, our preliminary results indicated that DOC treatment could increase the Reg IV mRNA expression of intestinal polys in APCmin/+ mice, but the underlying mechanism remains to be elucidated. So we aimed to investigate the possible role of Reg IV in the carcinogenesis of intestinal polyp promoted by DOC in APCmin/+ mice, including the effect on cell proliferation and apoptosis as well as signaling pathways. The accomplishment will assist in early prevention of colorectal cancer by targeting Reg IV.