REGULATION OF COX-2 IN INTESTINAL NEOPLASIA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dr. Dixon is atudying cyclooxygenases (specifically COX-2), which are central to prostaglandin biosynthesis and are intimately involved in inflammatory syndromes and in cancer. He has shown that HuR, an RNA binding protein that stabilizes COX-2 mRNA through interaction with the latters AU-rich region, is overexpressed in tumors. Dr. Dixon hypothesizes that high HuR levels promote COX-2 overproduction and tumorigenesis. He will determine if up-regulation of HuR leads to enhanced growth and tumorigenicity of cultured epithelial cells. In addition, he will assess the impact of transgenic HuR overproduction on COX-2 levels and tumor development in the mouse intestinal tract in vivo. Dr. Dixons studies should lead to a deeper understanding of the role of post-transcriptional regulation of COX-2 expression in tumor development in the intestinal tract.