Role of Cox-2 in Carcinogenesis
The Topham-Stafforini Lab has been a leader in studies of prostaglandins and related compounds. In experiments examining the regulation of cell growth, Prescott's group discovered marked shifts in the biochemical fate of arachidonic acid, which led to the identification and cloning of the human COX-2 gene. The lab was the first to clone an active form of this human gene. Studies have shown that the COX-2 enzyme is the rate-limiting step in colon carcinogenesis. The COX-2 enzyme is now the target for new therapeutic drugs.
The Topham-Stafforini Lab examined the COX-2 gene for polymorphisms that alter inherited predisposition to colon cancer and showed that expression of the gene is influenced strongly by post-transcriptional mechanisms that may be a central component of carcinogenesis. In addition, the lab showed that COX-2 acts pro-neoplastically, not only through production of prostaglandins, but by diverting unesterified arachidonic acid that would otherwise signal to promote cell death. Thus, this work on lipid messengers has led to new mechanistic insights and practical applications in a common cancer.