Journal Article

Enhancement of colon carcinogenesis by prostaglandin E<sub>2</sub> administration

Toshihiko Kawamori, Naoaki Uchiya, Takashi Sugimura and Keiji Wakabayashi

in Carcinogenesis

Volume 24, issue 5, pages 985-990
Published in print May 2003 | ISSN: 0143-3334
Published online May 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg033
Enhancement of colon carcinogenesis by prostaglandin E2 administration

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Although an accumulating body of evidence indicates that levels of prostaglandin E2 (PGE2) in human and rodent colon cancers are higher than those in surrounding normal tissues, the precise contribution of PGE2 to the process of colon cancer development has still been unclear. Therefore, we designed a study using a well-established azoxymethane (AOM)-induced colon carcinogenesis in male F344 rat model to investigate whether administration of exogenous PGE2 has a real impact on colon carcinogenesis. Intraperitoneal PGE2 injections (7.7 µg) once a week for 25 weeks significantly increased the AOM-induced colon tumor incidence (percent rats with tumors, 92 versus 53%, P < 0.05), especially adenocarcinomas (92 versus 47%, P < 0.05), and multiplicity (number of tumors per rat, 2.8 versus 1.0, P < 0.05). PGE2 treatment significantly increased 5-bromo-2′-deoxyuridine (BrdUrd) labeling index (11.8 versus 9.7%, P < 0.05) and reduced apoptotic index (0.34 versus 0.53%, P < 0.05) in colon cancers induced by AOM. PGE2 exhibits its physiological functions through binding to E-prostanoid (EP) membrane receptors EP1-4. All four types of EP receptors were detected in AOM-induced colon cancers using reverse transcription–polymerase chain reaction (RT–PCR). Our results provide evidence that PGE2 enhances colon carcinogenesis through induction of cell proliferation and reduction of apoptosis.

Keywords: ACF, aberrant crypt foci; AOM, azoxymethane; BrdUrd, 5-bromo-2′-deoxyuridine; COX, cyclooxygenase; EP, E-prostanoid; NSAID, non-steroidal anti-inflammatory drug; PG, prostaglandin; RT–PCR, reverse transcription–polymerase chain reaction

Journal Article.  4603 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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