Gene Deletion of Microsomal Prostaglandin E Synthase-1 Suppresses Chemically Induced Skin Carcinogenesis

Background/Aim: Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) is a terminal enzyme in PGE(2) synthesis and highly expressed in several cancers. In this study, to reveal the involvement of mPGES-1 in skin carcinogenesis, the effect of mPGES-1 deficiency on twostage skin carcinogenesis in mice was investigated. Materials and Methods: A two-stage skin carcinogenesis model using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter was applied on mPGES-1 knockout (KO) mice and littermate wild-type mice of a Balb/c genetic background. Results: DMBA/TPA- induced skin carcinogenesis was suppressed in mPGES-1 KO mice. The induction of IL-17 and other inflammatory cytokines by TPA was also suppressed by mPGES-1 deficiency, although DMBA-induced apoptosis was not affected. Conclusion: mPGES-1 promotes chemically induced skin carcinogenesis and might play an important role in the TPA-induced promotion phase of the two- stage skin carcinogenesis model. mPGES-1 inhibition may be a therapeutic target for skin cancer.

Automated summary

The study indicates that mPGES-1 plays an important role in skin carcinogenesis, with mPGES-1 deficiency suppressing DMBA/TPA-induced skin carcinogenesis and inhibiting the induction of inflammatory cytokines by TPA.