Cyclooxygenase-2 Overexpression in the Skin of Transgenic Mice Results in Suppression of Tumor Development

The study investigated the role of cyclooxygenase-2 (COX-2) in tumor development using transgenic mice that overexpressed COX-2 in their skin. These mice, known as K14.COX2, exhibited significant alopecia, which was reversible with a COX-2 inhibitor, indicating that hair loss was due to elevated COX-2 activity. Contrary to expectations, COX-2 overexpression protected the mice from skin tumor development, with K14.COX2 mice developing tumors at a much lower frequency compared to nontransgenic controls (3.3% vs. 93% on an FVB background and 25% vs. 100% on an ICR background). Additionally, these mice had significantly fewer tumors per mouse. The findings suggested that COX-2 and elevated prostaglandin levels might play a protective role against skin tumor development, challenging previous assumptions about COX-2's role in carcinogenesis.