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

In this study, transgenic mice overexpressing cyclooxygenase-2 (COX-2) in the skin, known as K14.COX2 mice, 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, these mice showed a marked resistance to skin tumor development, with a much lower tumor incidence and burden compared to nontransgenic controls. Specifically, tumor development was 3.3% in K14.COX2 mice versus 93% in controls on an FVB background, and 25% versus 100% on an ICR background. These findings suggested that COX-2 overexpression might protect against skin tumors, challenging the previously understood role of COX-2 in tumorigenesis.