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

Abstract

BACKGROUND/AIM:

Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) is a terminal enzyme in PGE2 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.

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.

• Authors: Yuka Sasaki, Hiroshi Kuwata, Eri Aida, Tsubasa Ochiai, Daisuke Kamei, Yoshihito Nakatani, Shuntaro Hara
• Journal: Anticancer research (Anticancer Res) Vol. 41 Issue 3 Pg. 1307-1314 (Mar 2021) ISSN: 1791-7530 [Electronic] Greece
• PMID: 33788722 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Cytokines
• 9,10-Dimethyl-1,2-benzanthracene
• Cyclooxygenase 2
• Prostaglandin-E Synthases
• Ptges protein, mouse
• Dinoprostone
• Tetradecanoylphorbol Acetate

Topics

• 9,10-Dimethyl-1,2-benzanthracene
• Animals
• Apoptosis (drug effects)
• Cyclooxygenase 2 (genetics)
• Cytokines (biosynthesis)
• Dinoprostone (analysis)
• Mice
• Mice, Inbred BALB C
• Prostaglandin-E Synthases (deficiency, genetics, physiology)
• Skin Neoplasms (chemically induced, prevention & control)
• Tetradecanoylphorbol Acetate