COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status.
COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status.
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DOI：
10.1186/1471-2407-11-238
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发表时间：
2011-06-13
期刊：
影响因子：
3.8
通讯作者：
Lundholm K
中科院分区：
文献类型：
--
作者：
Asting AG;Carén H;Andersson M;Lönnroth C;Lagerstedt K;Lundholm K
环氧合酶活性的增加促进结直肠癌的进展，但考克斯-2诱导的机制仍不清楚。因此，本研究旨在确定与结肠癌组织中高表达考克斯-2相关的外部细胞信号传导和转录因子。收集48例原发性结肠癌患者的肿瘤和正常结肠组织。定量肿瘤和正常结肠组织中的考克斯-2表达，包括对肿瘤mRNA的微阵列分析，解释高和低肿瘤考克斯-2表达。肿瘤组织与正常结肠组织进行交叉杂交。检测考克斯-2上游启动子区甲基化状态。与正常结肠相比，具有高考克斯-2表达的肿瘤在基因表达方面显示出较大差异。与低考克斯-2表达的肿瘤相比，高考克斯-2表达的肿瘤中出现了许多表达改变的基因。与低考克斯-2肿瘤患者的正常结肠相比，高考克斯-2肿瘤患者的正常结肠中的考克斯-2表达增加。IL 1 β、IL 6和iNOS转录物在细胞外信号传导因子中上调;在考克斯-2高表达的肿瘤中，9种转录因子（ATF 3、C/EBP、c-Fos、Fos-B、JDP 2、JunB、c-Maf、NF-κB、TCF 4）表达增加，5种转录因子（AP-2、CBP、Elk-1、p53、PEA 3）表达减少。考克斯-2基因启动子区在肿瘤组织和正常结肠组织中均未出现一致性甲基化。结肠癌组织中考克斯-2表达的协变量是转录因子和细胞外信号传导因子，但考克斯-2启动子区的DNA甲基化不是考克斯-2表达的重要因素。
Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.
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影响因子：
158.5
作者：
Sandler, RS;Halabi, S;Schilsky, R
通讯作者：
Schilsky, R
DOI：
10.1016/j.bbrc.2004.01.020
发表时间：
2004-02-27
影响因子：
3.1
作者：
Kim, SP;Park, JW;Kwon, TK
通讯作者：
Kwon, TK
影响因子：
6.4
作者：
Gustafsson, Annika;Hansson, Elisabeth;Lundholm, Kent
通讯作者：
Lundholm, Kent
DOI：
10.3816/cgc.2003.n.020
发表时间：
2003-09-01
期刊：
Clinical prostate cancer
影响因子：
--
作者：
Lin, Daniel W;Nelson, Peter S
通讯作者：
Nelson, Peter S
影响因子：
11.2
作者：
Grau, R;Iñiguez, MA;Fresno, M
通讯作者：
Fresno, M