Basic—Alimentary TractThe mRNA Binding Proteins HuR and Tristetraprolin Regulate Cyclooxygenase 2 Expression During Colon Carcinogenesis
Section snippets
Colorectal Tissue Specimens
Immunohistochemical analysis was performed on paraffin-embedded human tissue array samples obtained from 2 sources. The colorectal carcinoma progression tissue array (CHTN2003CRCprog) from the Cooperative Human Tissue Network (National Cancer Institute [NCI], Rockville, MD) contained 42 normal colorectal tissue samples derived from 14 cases of nonneoplastic colonic mucosa, 42 adenoma tissue samples derived from 14 cases of adenomatous polyps, and 42 adenocarcinoma tissue samples derived from 14
HuR, TTP, and COX-2 Protein Expression in Human Colorectal Tumorigenesis
We and others have shown increased HuR expression to occur in human colorectal tumors2, 3, 11; however, the state of TTP expression in colon cancer is not known. Based on the opposing effects these RNA-binding proteins elicit on ARE-containing gene expression, we sought to determine whether corresponding changes in HuR and TTP expression exist during colorectal tumorigenesis. HuR and TTP immunoreactivity were evaluated on serial sections of human tissue arrays containing adenocarcinomas,
Discussion
The control of COX-2 expression is a complex regulatory process that requires input from multiple pathways impacting gene expression on both transcriptional and posttranscriptional levels.10 It is generally well accepted that transcriptional activation of the COX-2 gene PTGS2 is an early event in tumorigenesis because evidence demonstrates the presence of COX-2 mRNA in virtually all colorectal adenomas, adenocarcinomas, and colon cancer cells.2, 10, 14, 15 However, the presence of COX-2 mRNA
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by grants P20 RR017698 from the National Institutes of Health, and RSG-06-122-01-CNE from the American Cancer Society (to D.A.D.).