Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: Ιmplications for cholangiocarcinogenesis

  • Authors:
    • Yasutaka Ishii
    • Tamito Sasaki
    • Masahiro Serikawa
    • Tomoyuki Minami
    • Akihito Okazaki
    • Masanobu Yukutake
    • Takashi Ishigaki
    • Keiichi Kosaka
    • Teruo Mouri
    • Satoshi Yoshimi
    • Akinori Shimizu
    • Tomofumi Tsuboi
    • Kazuaki Chayama
  • View Affiliations

  • Published online on: July 24, 2013     https://doi.org/10.3892/ijo.2013.2038
  • Pages: 1073-1079
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Abstract

Cholangiocarcinoma (CCA) occurs frequently in primary sclerosing cholangitis (PSC). Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) induced by inflammation are believed to mediate prostaglandin E2 (PGE2) production thereby promoting carcinogenesis. Their expression in PSC-associated CCA tissues and non-neoplastic bile duct epithelial cells (BDECs) in PSC was investigated. COX-2 and mPGES-1 levels in 15 PSC patients (7 with CCA) were scored using immunohistochemical staining. The results were compared with those obtained in CCA tissues and non-neoplastic BDECs (controls) of 15 sporadic CCA patients. Non-neoplastic BDECs from large and small bile ducts were investigated separately. The mRNA expression levels of COX-2 and mPGES-1 in CCA tissues were analyzed by quantitative polymerase chain reaction. Ki-67 immunostaining was performed to evaluate cell proliferation. COX-2 was strongly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC. This expression was significantly upregulated in both compared with sporadic CCA tissues and non-neoplastic BDECs in sporadic CCA (both P<0.01). mPGES-1 was expressed at moderate to strong levels in PSC. Compared with controls, the expression was significantly higher in non-neoplastic small BDECs (P<0.01). COX-2 mRNA levels were significantly higher in PSC-associated tissues than in sporadic CCA tissues (P<0.01). Conversely, no differences were observed in mPGES-1 mRNA levels. Ki-67 labeling indices were higher in PSC-associated CCA tissues and non-neoplastic BDECs in PSC than in controls. In conclusion, COX-2 and mPGES-1 were highly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC, suggesting the involvement of COX-2 and mPGES-1 in cholangiocarcinogenesis.
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October 2013
Volume 43 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ishii Y, Sasaki T, Serikawa M, Minami T, Okazaki A, Yukutake M, Ishigaki T, Kosaka K, Mouri T, Yoshimi S, Yoshimi S, et al: Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: Ιmplications for cholangiocarcinogenesis. Int J Oncol 43: 1073-1079, 2013.
APA
Ishii, Y., Sasaki, T., Serikawa, M., Minami, T., Okazaki, A., Yukutake, M. ... Chayama, K. (2013). Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: Ιmplications for cholangiocarcinogenesis. International Journal of Oncology, 43, 1073-1079. https://doi.org/10.3892/ijo.2013.2038
MLA
Ishii, Y., Sasaki, T., Serikawa, M., Minami, T., Okazaki, A., Yukutake, M., Ishigaki, T., Kosaka, K., Mouri, T., Yoshimi, S., Shimizu, A., Tsuboi, T., Chayama, K."Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: Ιmplications for cholangiocarcinogenesis". International Journal of Oncology 43.4 (2013): 1073-1079.
Chicago
Ishii, Y., Sasaki, T., Serikawa, M., Minami, T., Okazaki, A., Yukutake, M., Ishigaki, T., Kosaka, K., Mouri, T., Yoshimi, S., Shimizu, A., Tsuboi, T., Chayama, K."Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: Ιmplications for cholangiocarcinogenesis". International Journal of Oncology 43, no. 4 (2013): 1073-1079. https://doi.org/10.3892/ijo.2013.2038