1. ¹Department of Emergency Medicine, University of Rochester School of Medicine & Dentistry, Rochester, New York, USA
2. ²Departments of Pathology & Laboratory Medicine and Dermatology, Indiana University School of Medicine, Indianapolis, Indianapolis, USA
3. ³Department of Dermatology, University of Rochester School of Medicine & Dentistry, Rochester, New York, USA, Rochester, New York, USA
4. ⁴Department of Orthopedics, University of Rochester School of Medicine & Dentistry, Rochester, New York, USA
5. ⁵Department of Biostatistics, University of Rochester School of Medicine & Dentistry
6. ⁶Division of Nephrology and Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee, USA

Correspondence: Dr Alice P. Pentland, Department of Dermatology, 601 Elmwood Ave, Box 697, Rochester, NY, 14642. E-mail: alice_pentland@urmc.rochester.edu

Received 11 May 2006; Revised 10 July 2006; Accepted 21 July 2006; Published online 14 September 2006.

Abstract

Ultraviolet (UV) light is a complete carcinogen inducing and promoting squamous-cell carcinoma (SCC) of the skin. Recent work has shown that SCC initiation and promotion are enhanced by prostaglandin E₂ (PGE₂). PGE₂ interacts with specific EP receptors to regulate cellular functions. Previous work from our group has shown that the prostaglandin E₂ EP₂ receptor is a powerful regulator of keratinocyte growth. SKH-1 hairless mice lacking the EP₂ receptor were therefore studied to understand how this growth signaling pathway contributes to photocarcinogenesis. Our data indicate that UV-irradiated mice lacking EP₂ receptors exhibit decreased proliferation and a poor capacity for epidermal hypertrophy in response to UV injury. In a chronic irradiation model, these animals were protected from tumor formation, developing 50% fewer tumors than wild-type controls. Despite this capacity to protect against tumorigenesis, animals lacking EP₂ receptors grew tumors that were larger in size, with a more aggressive phenotype. Further study suggested that this susceptibility may be associated with synthesis of active metalloproteinase enzymes in greater quantities than keratinocytes expressing the EP₂ receptor, thereby enhancing the invasive potential of EP₂^-/- cells.