title: Prostaglandin E receptor EP3 deficiency modifies tumor outcome in mouse two-stage skin carcinogenesis.
abstract: We have recently shown that the prostaglandin E(2) (PGE(2)) receptor EP(3) plays an important role in suppression of colon cancer cell proliferation and that its deficiency enhances late stage colon carcinogenesis. Here we examined the effects of EP(3)-deficiency on two-stage skin carcinogenesis. 7,12-Dimethylbenz[a]anthracene (50 microg/200 microl of acetone) was thus applied to the back skin of female EP(3)-knockout and wild-type mice at 8 weeks of age, followed by treatment with 12-O-tetradecanoylphorbol-13-acetate (5 microg/200 microl of acetone) twice a week for 25 weeks. First tumor appearance was observed in EP(3)-knockout mice at week 10, which was 3 weeks later than in EP(3) wild-type mice, and multiplicity observed at week 11 was significantly lower in the EP(3)-knockout case. However, histological examination showed that the tumor incidence and multiplicity at week 25 were not significantly changed in knockout mice and wild-type mice (incidence, 19/19 versus 23/24; multiplicity, 3.58 +/- 0.51 versus 3.17 +/- 0.63, respectively). Interestingly, there were no squamous cell carcinomas (SCCs) in the EP(3)-knockout mice, while SCCs were observed in 3 out of 24 wild-type mice. Furthermore, benign keratoacanthomas only developed in EP(3)-knockout mice (6/19 versus 0/24, P < 0.01). The results suggest that PGE(2) receptor EP(3) signaling might contribute to development of SCCs in the skin.
authors.affiliation: Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shoji
authors.forename: Mami
authors.initials: M
authors.lastname: Takahashi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Takasuka
authors.forename: Naoko
authors.initials: N
authors.lastname: Niho
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kitamura
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Sato
authors.forename: Takayuki
authors.initials: T
authors.lastname: Maruyama
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugimura
authors.forename: Keiji
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005260:Female; D015994:Incidence; D007636:Keratoacanthoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000502:physiology*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D016896:Treatment Outcome
chemical_list: D015820:Cadherins; C545648:Ptger3 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate