Identification of the IFITM family as a new molecular marker in human colorectal tumors
Identification of the IFITM family as a new molecular marker in human colorectal tumors
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DOI：
10.1158/0008-5472.can-05-2731
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发表时间：
2006-02-15
期刊：
影响因子：
11.2
通讯作者：
Romagnolo, B
中科院分区：
文献类型：
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作者：
Andreu, P;Colnot, S;Romagnolo, B
我们分析了一个新的小鼠家族性腺瘤性息肉病模型（APC（Δ 14/+））的肠腺瘤的表达谱，使用抑制性消减杂交，以确定新的诊断标志物的结直肠癌发生。我们确定了18个候选基因在腺瘤中的表达水平增加。随后的北方印迹，实时逆转录-PCR和原位杂交分析证实了它们在β-连环蛋白激活的小鼠腺瘤上皮细胞中的诱导作用。我们发现，大多数基因在人类结肠腺瘤和癌中的表达水平也发生了改变。我们专注于IFITM基因编码IFN诱导的跨膜蛋白。基因表达水平的系列分析显示，在小鼠和人类的早期和晚期肠道肿瘤中表达水平较高。使用Apc失活的条件性小鼠模型和人结肠癌细胞系，我们表明IFITM基因表达在β-连环蛋白信号转导激活后被快速诱导。通过对人类肿瘤的大规模分析，我们发现IFITM基因表达在结直肠肿瘤中特异性显著上调，因此可能是这些肿瘤的有用诊断工具。
We analyzed the expression profiles of intestinal adenomas from a new murine familial adenomatous polyposis model (Apc(Delta 14/+)) using suppression subtractive hybridization to identify novel diagnostic markers of colorectal carcinogenesis. We identified 18 candidate genes having increased expression levels in the adenoma. Subsequent Northern blotting, real-time reverse transcription-PCR, and in situ hybridization analysis confirmed their induction in beta-catenin-activated epithelial cells of murine adenomas. We showed that most of the genes also have altered expression levels in human colonic adenomas and carcinomas. We focused on the IFITM genes that encode IFN-inducible transmembrane proteins. Serial analyses of gene expression levels revealed high levels of expression in early and late intestinal neoplasm in both mice and humans. Using a conditional mouse model of Apc inactivation and a human colon carcinoma cell line, we showed that IFITM gene expression is rapidly induced after activation of the beta-catenin signaling. Using a large-scale analysis of human tumors, we showed that IFITM gene expression is significantly up-regulated specifically in colorectal tumors and thus may be a useful diagnostic tool in these tumors.