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

被引:32
作者
Brouxhon, Sabine
Konger, Raymond L.
VanBuskirk, JoAnne
Sheu, Tzong-jen
Ryan, Julie
Erdle, Brandon
Almudevar, Anthony
Breyer, Richard M.
Scott, Glynis
Pentland, Alice P.
机构
[1] Univ Rochester, Sch Med & Dent, Dept Dermatol, Rochester, NY 14642 USA
[2] Univ Rochester, Sch Med & Dent, Dept Emergency Med, New York, NY USA
[3] Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN USA
[4] Indiana Univ, Sch Med, Dept Lab Med, Indianapolis, IN USA
[5] Indiana Univ, Sch Med, Dept Dermatol, Indianapolis, IN USA
[6] Univ Rochester, Sch Med & Dent, Dept Orthoped, Rochester, NY USA
[7] Vanderbilt Univ, Div Nephrol, Nashville, TN USA
[8] Vanderbilt Univ, Dept Med & Pharmacol, Nashville, TN USA
[9] Univ Rochester, Sch Med & Dent, Dept Biostat, Rochester, NY 14627 USA
关键词
D O I
10.1038/sj.jid.5700547
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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 E-2 (PGE(2)). PGE(2) interacts with specific EP receptors to regulate cellular functions. Previous work from our group has shown that the prostaglandin E-2 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.
引用
收藏
页码:439 / 446
页数:8
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