Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness

Sabine Brouxhon, Raymond L. Konger, Jo Anne VanBuskirk, Tzong Jen Sheu, Julie Ryan, Brandon Erdle, Anthony Almudevar, Richard M. Breyer, Glynis Scott, Alice P. Pentland

Research output: Contribution to journalArticle

34 Scopus citations

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 (PGE 2). 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 EP 2 -/- cells.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalJournal of Investigative Dermatology
Volume127
Issue number2
DOIs
StatePublished - Feb 1 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Brouxhon, S., Konger, R. L., VanBuskirk, J. A., Sheu, T. J., Ryan, J., Erdle, B., Almudevar, A., Breyer, R. M., Scott, G., & Pentland, A. P. (2007). Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness. Journal of Investigative Dermatology, 127(2), 439-446. https://doi.org/10.1038/sj.jid.5700547