Interplay of insulin-like growth factor-II, insulin-like growth factor-I, insulin-like growth factor-I receptor, COX-2, and matrix metalloproteinase-7, play key roles in the early stage of colorectal carcinogenesis
Interplay of insulin-like growth factor-II, insulin-like growth factor-I, insulin-like growth factor-I receptor, COX-2, and matrix metalloproteinase-7, play key roles in the early stage of colorectal carcinogenesis
复制标题
DOI：
10.1158/1078-0432.ccr-04-0875
复制
发表时间：
2004-12-01
影响因子：
11.5
通讯作者：
Imai, K
中科院分区：
文献类型：
--
作者：
Nosho, K;Yamamoto, H;Imai, K
目的：本研究的目的是描述胰岛素样生长因子（IGF）-II表达与IGF-I、IGF-I受体（IGF-IR）、环氧合酶-2（考克斯-2）和基质金属蛋白酶（MMP）-7在早期结直肠癌发生中的关系。采用半定量逆转录酶-PCR技术，对90例人结直肠肿瘤组织进行检测分析了63例腺瘤和27例粘膜下pT 1癌的IGF-II、IGF-IR、IGF-I、考克斯-2和MMP-7表达。还对99例腺瘤组织和60例pT 1癌组织进行了IGF-II表达的免疫组化分析。分析IGF-II基因印迹的丢失。结果：90例大肠癌组织中IGF-Ⅱ mRNA表达阳性率为37.8%。IGF-Ⅱ mRNA在pT 1癌中的表达率（70.4%）明显高于腺瘤（23.8%）。免疫组化IGF-II表达也更频繁地检测到pT 1癌（58.3%）比腺瘤（25.3%）。在IGF-II过表达的34个结直肠肿瘤中，有15个（44.1%）观察到IGF-II基因印迹缺失。IGF-II表达与IGF-IR、IGF-I表达呈正相关。考克斯-2和MMP-7 mRNA表达阳性率分别为42.2%和77.8%，且均与IGF-I、IGF-II和IGF-IR表达呈正相关。结论：IGF-II与IGF-IR、IGF-I、考克斯-2、MMP-7共同参与大肠癌的发生发展，在大肠癌的发生发展中起重要作用。
Purpose: The aim of this study was to characterize the relationship of insulin-like growth factor (IGF)-II expression with IGF-I, IGF-I receptor (IGF-IR), cyclooxygenase-2 (COX-2), and matrix metalloproteinase (MMP)-7 in early colorectal carcinogenesis.Experimental Design: With the semiquantitative reverse transcriptase-PCR, 90 human colorectal tumor tissues (63 adenomas and 27 submucosal pT1 cancers) were analyzed for IGF-II, IGF-IR, IGF-I, COX-2, and MMP-7 expression. Ninety-nine adenoma tissues and 60 pT1 cancer tissues were also analyzed immunohistochemically for IGF-II expression. Loss of imprinting of the IGF-II gene was analyzed. Paired carcinoma and adenoma tissues obtained from a carcinoma in adenoma lesion was analyzed by a cDNA array.Results: IGF-II mRNA expression was detected in 37.8% of the 90 colorectal tumor tissues. The frequency of IGF-II mRNA expression was significantly higher in pT1 cancer (70.4%) than in adenoma (23.8%). Immunohistochemical IGF-II expression was also more frequently detected in pT1 cancer (58.3%) than in adenoma (25.3%). Loss of imprinting of the IGF-II gene was observed in 15 (44.1%) of the 34 colorectal tumors in which IGF-II was overexpressed. IGF-II expression was positively correlated with the expression of lGF-IR and IGF-I. COX-2 and MMP-7 mRNA expression was detected in 42.2% and 77.8% of the tumor tissues, respectively, and both were positively correlated with IGF-I, IGF-II, and IGF-IR expression. IGF-II was the most differentially expressed gene between carcinoma and adenoma lesions.Conclusions: IGF-II, in conjunction with IGF-IR, IGF-I, COX-2, and MMP-7, seems to play a key role in the early stage of colorectal carcinogenesis.