Author:
Asting Annika Gustafsson,Carén Helena,Andersson Marianne,Lönnroth Christina,Lagerstedt Kristina,Lundholm Kent
Abstract
Abstract
Background
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.
Method
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.
Results
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.
Conclusions
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.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference35 articles.
1. Greenhough A, Smartt HJ, Moore AE, Roberts HR, Williams AC, Paraskeva C, Kaidi A: The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis. 2009, 30 (3): 377-386. 10.1093/carcin/bgp014.
2. Gustafsson A, Hansson E, Kressner U, Nordgren S, Andersson M, Wang W, Lonnroth C, Lundholm K: EP1-4 subtype, COX and PPAR gamma receptor expression in colorectal cancer in prediction of disease-specific mortality. Int J Cancer. 2007, 121 (2): 232-240. 10.1002/ijc.22582.
3. Gustafsson A, Hansson E, Kressner U, Nordgren S, Andersson M, Lonnroth C, Lundholm K: Prostanoid receptor expression in colorectal cancer related to tumor stage, differentiation and progression. Acta Oncol. 2007, 1-6.
4. Cahlin C, Gelin J, Andersson M, Lonnroth C, Lundholm K: The effects of non-selective, preferential-selective and selective COX-inhibitors on the growth of experimental and human tumors in mice related to prostanoid receptors. Int J Oncol. 2005, 27 (4): 913-923.
5. Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW: Aspirin use and risk of fatal cancer. Cancer Res. 1993, 53 (6): 1322-1327.
Cited by
46 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献