Skip to main content
Erschienen in: Virchows Archiv 6/2009

01.06.2009 | Original Article

Microsomal prostaglandin E synthase protein levels correlate with prognosis in colorectal cancer patients

verfasst von: Tsuguhiko Seo, Atsushi Tatsuguchi, Seiichi Shinji, Masaoki Yonezawa, Keigo Mitsui, Shu Tanaka, Shunji Fujimori, Katya Gudis, Yuh Fukuda, Choitsu Sakamoto

Erschienen in: Virchows Archiv | Ausgabe 6/2009

Einloggen, um Zugang zu erhalten

Abstract

The aim of this study is to investigate the expression of three prostaglandin E synthase (PGES) isomers in colorectal cancer (CRC) tissue and to evaluate their relationship to clinicopathological factors and patient prognosis. Microsomal PGES (mPGES)-1, mPGES-2, cytosolic PGES (cPGES) and cyclooxygenase (COX)-2 protein expression were analyzed by real-time polymerase chain reaction and Western blot. The localization of each PGES and COX-2 protein was examined by immunohistochemistry in 155 surgical resections and correlated to clinicopathological factors and patient prognosis. mPGES-1 mRNA and protein levels were significantly higher in CRC than in paired normal tissues. mPGES-1 immunoreactivity localized in cancer cells in 43% of cases. mPGES-2 immunoreactivity was significantly more pronounced in cancer cells than in adjacent normal epithelium in 36% of cases. cPGES immunoreactivity was homogeneous in cancer cells and thus determined constitutive. mPGES-1 and mPGES-2 correlated with significantly worse prognosis in stage I–III patients. These results indicate that mPGES-1 and mPGES-2 may each play a role in CRC progression.
Literatur
1.
Zurück zum Zitat Ulrich CM, Bigler J, Potter JD (2006) Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer 6:130–140PubMedCrossRef Ulrich CM, Bigler J, Potter JD (2006) Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer 6:130–140PubMedCrossRef
2.
Zurück zum Zitat Sinicrope FA, Gill S (2004) Role of cyclooxygenase-2 in colorectal cancer. Cancer Metastasis Rev 23:63–75PubMedCrossRef Sinicrope FA, Gill S (2004) Role of cyclooxygenase-2 in colorectal cancer. Cancer Metastasis Rev 23:63–75PubMedCrossRef
3.
Zurück zum Zitat Kawamori T, Rao CV, Seibert K et al (1998) Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 58:409–412PubMed Kawamori T, Rao CV, Seibert K et al (1998) Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 58:409–412PubMed
4.
Zurück zum Zitat Rahme E, Barkun AN, Toubouti Y et al (2003) The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence. Gastroenterology 125:404–412PubMedCrossRef Rahme E, Barkun AN, Toubouti Y et al (2003) The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence. Gastroenterology 125:404–412PubMedCrossRef
5.
Zurück zum Zitat Bertagnolli MM, Eagle CJ, Zauber AG et al (2006) Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 355:873–884PubMedCrossRef Bertagnolli MM, Eagle CJ, Zauber AG et al (2006) Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 355:873–884PubMedCrossRef
6.
Zurück zum Zitat Arber N, Eagle CJ, Spicak J et al (2006) Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 355:885–895PubMedCrossRef Arber N, Eagle CJ, Spicak J et al (2006) Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 355:885–895PubMedCrossRef
7.
Zurück zum Zitat Chan AT, Ogino S, Fuchs CS (2007) Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 356:2131–2142PubMedCrossRef Chan AT, Ogino S, Fuchs CS (2007) Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 356:2131–2142PubMedCrossRef
8.
Zurück zum Zitat Sinicrope FA (2006) Targeting cyclooxygenase-2 for prevention and therapy of colorectal cancer. Mol Carcinog 45:447–454PubMedCrossRef Sinicrope FA (2006) Targeting cyclooxygenase-2 for prevention and therapy of colorectal cancer. Mol Carcinog 45:447–454PubMedCrossRef
10.
Zurück zum Zitat Jakobsson PJ, Thoren S, Morgenstern R et al (1999) Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A 96:7220–7225PubMedCrossRef Jakobsson PJ, Thoren S, Morgenstern R et al (1999) Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A 96:7220–7225PubMedCrossRef
11.
Zurück zum Zitat Tanioka T, Nakatani Y, Semmyo N et al (2000) Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. J Biol Chem 275:32775–32782PubMedCrossRef Tanioka T, Nakatani Y, Semmyo N et al (2000) Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 biosynthesis. J Biol Chem 275:32775–32782PubMedCrossRef
12.
Zurück zum Zitat Tanikawa N, Ohmiya Y, Ohkubo H et al (2002) Identification and characterization of a novel type of membrane-associated prostaglandin E synthase. Biochem Biophys Res Commun 291:884–889PubMedCrossRef Tanikawa N, Ohmiya Y, Ohkubo H et al (2002) Identification and characterization of a novel type of membrane-associated prostaglandin E synthase. Biochem Biophys Res Commun 291:884–889PubMedCrossRef
13.
Zurück zum Zitat Han R, Tsui S, Smith TJ (2002) Up-regulation of prostaglandin E2 synthesis by interleukin-1beta in human orbital fibroblasts involves coordinate induction of prostaglandin-endoperoxide H synthase-2 and glutathione-dependent prostaglandin E2 synthase expression. J Biol Chem 277:16355–16364PubMedCrossRef Han R, Tsui S, Smith TJ (2002) Up-regulation of prostaglandin E2 synthesis by interleukin-1beta in human orbital fibroblasts involves coordinate induction of prostaglandin-endoperoxide H synthase-2 and glutathione-dependent prostaglandin E2 synthase expression. J Biol Chem 277:16355–16364PubMedCrossRef
14.
Zurück zum Zitat Murakami M, Naraba H, Tanioka T et al (2000) Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem 275:32783–32792PubMedCrossRef Murakami M, Naraba H, Tanioka T et al (2000) Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem 275:32783–32792PubMedCrossRef
15.
Zurück zum Zitat Murakami M, Nakashima K, Kamei D et al (2003) Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2. J Biol Chem 278:37937–37947PubMedCrossRef Murakami M, Nakashima K, Kamei D et al (2003) Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2. J Biol Chem 278:37937–37947PubMedCrossRef
16.
Zurück zum Zitat Yoshimatsu K, Golijanin D, Paty PB et al (2001) Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer. Clin Cancer Res 7:3971–3976PubMed Yoshimatsu K, Golijanin D, Paty PB et al (2001) Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer. Clin Cancer Res 7:3971–3976PubMed
17.
Zurück zum Zitat van Rees BP, Sabula A, Thorne S et al (2003) Expression of microsomal prostaglandin E synthase-1 in intestinal type gastric adenocarcinoma and in gastric cancer cell lines. Int J Cancer 107:551–556PubMedCrossRef van Rees BP, Sabula A, Thorne S et al (2003) Expression of microsomal prostaglandin E synthase-1 in intestinal type gastric adenocarcinoma and in gastric cancer cell lines. Int J Cancer 107:551–556PubMedCrossRef
18.
Zurück zum Zitat Mehrotra S, Morimiya A, Agarwal B et al (2006) Microsomal prostaglandin E2 synthase-1 in breast cancer: a potential target for therapy. J Pathol 208:356–363PubMedCrossRef Mehrotra S, Morimiya A, Agarwal B et al (2006) Microsomal prostaglandin E2 synthase-1 in breast cancer: a potential target for therapy. J Pathol 208:356–363PubMedCrossRef
19.
Zurück zum Zitat Rask K, Zhu Y, Wang W et al (2006) Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression. Mol Cancer 5:62PubMedCrossRef Rask K, Zhu Y, Wang W et al (2006) Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression. Mol Cancer 5:62PubMedCrossRef
20.
Zurück zum Zitat Gudis K, Tatsuguchi A, Wada K et al (2007) Clinical significance of prostaglandin E synthase expression in gastric cancer tissue. Hum Pathol 38:1826–1835PubMedCrossRef Gudis K, Tatsuguchi A, Wada K et al (2007) Clinical significance of prostaglandin E synthase expression in gastric cancer tissue. Hum Pathol 38:1826–1835PubMedCrossRef
21.
Zurück zum Zitat Nakanishi M, Montrose DC, Clark P et al (2008) Genetic deletion of mPGES-1 suppresses intestinal tumorigenesis. Cancer Res 68:3251–3259PubMedCrossRef Nakanishi M, Montrose DC, Clark P et al (2008) Genetic deletion of mPGES-1 suppresses intestinal tumorigenesis. Cancer Res 68:3251–3259PubMedCrossRef
22.
Zurück zum Zitat Kamei D, Murakami M, Nakatani Y et al (2003) Potential role of microsomal prostaglandin E synthase-1 in tumorigenesis. J Biol Chem 278:19396–19405PubMedCrossRef Kamei D, Murakami M, Nakatani Y et al (2003) Potential role of microsomal prostaglandin E synthase-1 in tumorigenesis. J Biol Chem 278:19396–19405PubMedCrossRef
23.
Zurück zum Zitat Gudis K, Tatsuguchi A, Wada K et al (2005) Microsomal prostaglandin E synthase (mPGES)-1, mPGES-2 and cytosolic PGES expression in human gastritis and gastric ulcer tissue. Lab Invest 85:225–236PubMedCrossRef Gudis K, Tatsuguchi A, Wada K et al (2005) Microsomal prostaglandin E synthase (mPGES)-1, mPGES-2 and cytosolic PGES expression in human gastritis and gastric ulcer tissue. Lab Invest 85:225–236PubMedCrossRef
24.
Zurück zum Zitat Guo H, Tatsuguchi A, Shinji S et al (2006) Cyclooxygenase-2 expression correlates with membrane-type-1 matrix metalloproteinase expression in colorectal cancer tissue. Dis Colon Rectum 49:1184–1192PubMedCrossRef Guo H, Tatsuguchi A, Shinji S et al (2006) Cyclooxygenase-2 expression correlates with membrane-type-1 matrix metalloproteinase expression in colorectal cancer tissue. Dis Colon Rectum 49:1184–1192PubMedCrossRef
25.
Zurück zum Zitat Tatsuguchi A, Kishida T, Fujimori S et al (2006) Differential expression of cyclo-oxygenase-2 and nuclear beta-catenin in colorectal cancer tissue. Aliment Pharmacol Ther 24(Suppl 4):153–159 Tatsuguchi A, Kishida T, Fujimori S et al (2006) Differential expression of cyclo-oxygenase-2 and nuclear beta-catenin in colorectal cancer tissue. Aliment Pharmacol Ther 24(Suppl 4):153–159
26.
Zurück zum Zitat Stichtenoth DO, Thoren S, Bian H et al (2001) Microsomal prostaglandin E synthase is regulated by proinflammatory cytokines and glucocorticoids in primary rheumatoid synovial cells. J Immunol 167:469–474PubMed Stichtenoth DO, Thoren S, Bian H et al (2001) Microsomal prostaglandin E synthase is regulated by proinflammatory cytokines and glucocorticoids in primary rheumatoid synovial cells. J Immunol 167:469–474PubMed
27.
Zurück zum Zitat Fux R, Schwab M, Thon KP et al (2005) Cyclooxygenase-2 expression in human colorectal cancer is unrelated to overall patient survival. Clin Cancer Res 11:4754–4760PubMedCrossRef Fux R, Schwab M, Thon KP et al (2005) Cyclooxygenase-2 expression in human colorectal cancer is unrelated to overall patient survival. Clin Cancer Res 11:4754–4760PubMedCrossRef
28.
Zurück zum Zitat Tsujii M, Kawano S, Tsuji S et al (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705–716PubMedCrossRef Tsujii M, Kawano S, Tsuji S et al (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705–716PubMedCrossRef
29.
Zurück zum Zitat Tatsuguchi A, Matsui K, Shinji Y et al (2004) Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue. Hum Pathol 35:488–495PubMedCrossRef Tatsuguchi A, Matsui K, Shinji Y et al (2004) Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue. Hum Pathol 35:488–495PubMedCrossRef
30.
Zurück zum Zitat Tanaka S, Tatsuguchi A, Futagami S et al (2006) Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma. Gut 55:54–61PubMedCrossRef Tanaka S, Tatsuguchi A, Futagami S et al (2006) Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma. Gut 55:54–61PubMedCrossRef
31.
Zurück zum Zitat Kudo I, Murakami M (2005) Prostaglandin e synthase, a terminal enzyme for prostaglandin E2 biosynthesis. J Biochem Mol Biol 38:633–638PubMed Kudo I, Murakami M (2005) Prostaglandin e synthase, a terminal enzyme for prostaglandin E2 biosynthesis. J Biochem Mol Biol 38:633–638PubMed
32.
Zurück zum Zitat Watanabe K, Ohkubo H, Niwa H et al (2003) Essential 110Cys in active site of membrane-associated prostaglandin E synthase-2. Biochem Biophys Res Commun 306:577–581PubMedCrossRef Watanabe K, Ohkubo H, Niwa H et al (2003) Essential 110Cys in active site of membrane-associated prostaglandin E synthase-2. Biochem Biophys Res Commun 306:577–581PubMedCrossRef
33.
Zurück zum Zitat Hu J, Meng Q, Roy SK et al (2002) A Novel Transactivating Factor That Regulates Interferon-gamma-dependent Gene Expression. J Biol Chem 277:30253–30263PubMedCrossRef Hu J, Meng Q, Roy SK et al (2002) A Novel Transactivating Factor That Regulates Interferon-gamma-dependent Gene Expression. J Biol Chem 277:30253–30263PubMedCrossRef
34.
Zurück zum Zitat Wright KL, Weaver SA, Patel K et al (2004) Differential regulation of prostaglandin E biosynthesis by interferon-gamma in colonic epithelial cells. Br J Pharmacol 141:1091–1097PubMedCrossRef Wright KL, Weaver SA, Patel K et al (2004) Differential regulation of prostaglandin E biosynthesis by interferon-gamma in colonic epithelial cells. Br J Pharmacol 141:1091–1097PubMedCrossRef
35.
Zurück zum Zitat Bresalier RS, Sandler RS, Quan H et al (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–1102PubMedCrossRef Bresalier RS, Sandler RS, Quan H et al (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–1102PubMedCrossRef
36.
Zurück zum Zitat Cheng Y, Wang M, Yu Y et al (2006) Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function. J Clin Invest 116:1391–1399PubMedCrossRef Cheng Y, Wang M, Yu Y et al (2006) Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function. J Clin Invest 116:1391–1399PubMedCrossRef
37.
Zurück zum Zitat Elander N, Ungerbäck J, Olsson H et al (2008) Genetic deletion of mPGES-1 accelerates intestinal tumorigenesis in APC(Min/+) mice. Biochem Biophys Res Commun 372:249–253PubMedCrossRef Elander N, Ungerbäck J, Olsson H et al (2008) Genetic deletion of mPGES-1 accelerates intestinal tumorigenesis in APC(Min/+) mice. Biochem Biophys Res Commun 372:249–253PubMedCrossRef
Metadaten
Titel
Microsomal prostaglandin E synthase protein levels correlate with prognosis in colorectal cancer patients
verfasst von
Tsuguhiko Seo
Atsushi Tatsuguchi
Seiichi Shinji
Masaoki Yonezawa
Keigo Mitsui
Shu Tanaka
Shunji Fujimori
Katya Gudis
Yuh Fukuda
Choitsu Sakamoto
Publikationsdatum
01.06.2009
Verlag
Springer-Verlag
Erschienen in
Virchows Archiv / Ausgabe 6/2009
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-009-0777-z

Weitere Artikel der Ausgabe 6/2009

Virchows Archiv 6/2009 Zur Ausgabe

Neu im Fachgebiet Pathologie

Open Access 15.04.2024 | Biomarker | Schwerpunkt: Next Generation Pathology

Molekularpathologische Untersuchungen im Wandel der Zeit

11.04.2024 | Pathologie | Schwerpunkt: Next Generation Pathology

Vergleichende Pathologie in der onkologischen Forschung

Open Access 08.04.2024 | GIST | CME

Gastrointestinale Stromatumoren

Wo stehen wir?

03.04.2024 | Zielgerichtete Therapie | Schwerpunkt: Next Generation Pathology

Personalisierte Medizin in der Onkologie