Journal Article

Prostaglandin E receptor subtype EP<sub>1</sub> deficiency inhibits colon cancer development

Toshihiko Kawamori, Tomohiro Kitamura, Kouji Watanabe, Naoaki Uchiya, Takayuki Maruyama, Shuh Narumiya, Takashi Sugimura and Keiji Wakabayashi

in Carcinogenesis

Volume 26, issue 2, pages 353-357
Published in print February 2005 | ISSN: 0143-3334
Published online February 2005 | e-ISSN: 1460-2180 | DOI:
Prostaglandin E receptor subtype EP1 deficiency inhibits colon cancer development

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Prostaglandin E2 exerts its biological activity through binding to its membrane receptors, E-prostanoid (EP) receptors1–4. Our previous finding that lack of EP1 receptor inhibits the early stages of colon carcinogenesis led us to investigate whether EP1 receptor deficiency reduces colon cancer development induced by azoxymethane (AOM) using EP1 receptor knockout mice. At 6 weeks of age 33 homozygous EP1-deficient (EP1−/−) mice and 28 wild-type (EP1+/+) mice were given i.p. AOM (10 mg/kg body wt) once a week for 6 weeks. At 56 weeks of age all animals were killed and intestinal tumors were examined. The results clearly indicated that lack of EP1 receptor significantly reduced colon cancer incidence (27 versus 57%, P < 0.05) and multiplicity (0.30 versus 0.76, P < 0.05) as well as tumor volume (12.2 versus 75.6 mm3, P < 0.05). In EP1−/− mice, silver stained nucleolar organization region protein count as cell proliferation marker was significantly reduced (1.35 versus 2.17, P < 0.001) and apoptosis was significantly increased (0.685 versus 0.077, P < 0.001) in colon tumors induced by AOM compared with those in EP1+/+ mice. We confirmed that EP1 receptor mRNA was overexpressed in colon cancers of EP1+/+ mice using reverse transcription–polymerase chain reaction. These results provide strong evidence that the EP1 receptor is of major importance for colon cancer development and it could be a new target for a mechanism-based chemoprevention strategy against colon cancer development.

Keywords: AgNOR, silver stained nucleolar organizer region protein; AOM, azoxymethane; COX, cyclooxygenase; EP, E-prostanoid; NORs, nucleolar organizer regions; PGE2, prostaglandin E2; PKN, protein kinase N; RT-PCR, reverse transcription–polymerase chain reaction

Journal Article.  4091 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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