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.
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Authors | Yutaka Shoji, Mami Takahashi, Nobuo Takasuka, Naoko Niho, Tomohiro Kitamura, Hidetaka Sato, Takayuki Maruyama, Yukihiko Sugimoto, Shuh Narumiya, Takashi Sugimura, Keiji Wakabayashi |
Journal | Carcinogenesis
(Carcinogenesis)
Vol. 26
Issue 12
Pg. 2116-22
(Dec 2005)
ISSN: 0143-3334 [Print] England |
PMID | 16051640
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cadherins
- Ptger3 protein, mouse
- RNA, Messenger
- Receptors, Prostaglandin E
- Receptors, Prostaglandin E, EP3 Subtype
- 9,10-Dimethyl-1,2-benzanthracene
- Tetradecanoylphorbol Acetate
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Topics |
- 9,10-Dimethyl-1,2-benzanthracene
(toxicity)
- Animals
- Cadherins
(metabolism)
- Carcinoma, Squamous Cell
(chemically induced, metabolism, pathology)
- Female
- Incidence
- Keratoacanthoma
(chemically induced, metabolism, pathology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- RNA, Messenger
(genetics, metabolism)
- Receptors, Prostaglandin E
(genetics, physiology)
- Receptors, Prostaglandin E, EP3 Subtype
- Reverse Transcriptase Polymerase Chain Reaction
- Skin Neoplasms
(chemically induced, metabolism, pathology)
- Tetradecanoylphorbol Acetate
(toxicity)
- Treatment Outcome
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