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

• Published in: Anticancer research Vol. 41; no. 3; pp. 1307 - 1314
• Main Authors: Sasaki, Yuka, Kuwata, Hiroshi, Aida, Eri, Ochiai, Tsubasa, Kamei, Daisuke, Nakatani, Yoshihito, Hara, Shuntaro
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.03.2021
• Subjects: 12-O-Tetradecanoylphorbol-13-acetate; 9,10-Dimethyl-1,2-benzanthracene; Acetic acid; Animals; Anthracene; Apoptosis; Apoptosis - drug effects; Cancer; Carcinogenesis; Carcinogens; Cyclooxygenase 2 - genetics; Cytokines; Cytokines - biosynthesis; Dinoprostone - analysis; Gene deletion; Inflammation; Interleukin 17; Mice; Mice, Inbred BALB C; Prostaglandin E; Prostaglandin E2; Prostaglandin-E synthase; Prostaglandin-E Synthases - deficiency; Prostaglandin-E Synthases - genetics; Prostaglandin-E Synthases - physiology; Skin cancer; Skin Neoplasms - chemically induced; Skin Neoplasms - prevention & control; Tetradecanoylphorbol Acetate; Therapeutic targets; mPGES-1; skin carcinogenesis; inflammation; prostaglandin E2
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14888

Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) is a terminal enzyme in PGE 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 two-stage skin carcinogenesis in mice was investigated. 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. 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. 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.