A mechanism of COX-2 excess in tumors

Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostaglandin biosynthesis with a potential role in promoting colon carcinogenesis, but the mechanism of COX-2 overexpression remains unknown. In December 1 Journal of Clinical Investigation, Dan Dixon and colleagues from University of Utah, Salt Lake City, USA, show that altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells.

The COX-2 mRNA carries an A/U-rich element (ARE), a cis-acting RNA-destabilizing sequence which controls COX-2 mRNA stability. Dixon et al. used two different human colon carcinoma cell lines and observed that RNA-stability factor HuR (which binds to the COX-2 ARE) is overexpressed in more aggressive tumors cells and caused elevated expression of COX-2, VEGF and IL-8 (J Clin Invest 2001, 108:1657-1665).

These results provide a mechanism to link the control of COX-2 expression at a posttranscriptional level and tumorigenesis. In the light of...