DOI QR코드

DOI QR Code

Expression and Significance of Microsomal Prostaglandin Synthase-1 (mPGES-1) and Beclin-1 in the Development of Prostate Cancer

  • Xu, Lu-Wei (Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University) ;
  • Qian, Ming (Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University) ;
  • Jia, Rui-Peng (Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University) ;
  • Xu, Zheng (Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University) ;
  • Wu, Jian-Ping (Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University) ;
  • Li, Wen-Cheng (Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University) ;
  • Huang, Wen-Bin (Department of Pathology, Nanjing First Hospital Affiliated to Nanjing Medical University) ;
  • Chen, Xing-Guo (Center of Lab, Nanjing First Hospital Affiliated to Nanjing Medical University)
  • Published : 2012.04.30

Abstract

The aim of this study was to investigate the expression and significance of microsomal prostaglandin synthase-1 (mPGES-1) and Beclin-1 in the development of prostate cancer (PCa). Immunohistochemistry was performed on paraffin-embedded sections with rabbit polyclonal against mPGES-1 and Beclin-1 in 40 PCa, 40 benign prostatic hyperplasia (BPH) and 10 normal prostate specimens for this purpose. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for mRNA expression of mPGES-1 and Beclin-1, while MTT assays were used to ascertain the best working concentration of the mPGES-1 inhibitor (CAY10526). The effect of CAY10526 treatment on expression of Beclin-1 in DU-145 cells was studied using Western blot analysis. Localization of Beclin-1 and mPGES-1 was in endochylema. Significant differences in expression was noted among PCa, BPH and normal issues (P<0.05). Beclin-1 expression inversely correlated with mPGES-1 expression in PCa tissue (P<0.05). CAY10526 could significantly block mPGES-1 expression and the proliferation of DU-145 cells (P<0.05), while increasing Beclin-1 levels (P<0.05). Overexpression of mPGES-1 could decrease the autophagic PCa cell death. Inhibiting the expression of mPGES-1 may lead to DU-145 cell death and up-regulation of Beclin-1. The results suggest that inhibition of mPGES-1 may have therapeutic potential for PCa in the future.

Keywords

References

  1. Banning A, Florian S, Deubel S, et al (2008). GPx2 counteracts PGE2 production by dampening COX-2 and mPGES-1 expression in human colon cancer cells. Antioxid Redox Signal, 10, 1491-500. https://doi.org/10.1089/ars.2008.2047
  2. Beales IL, Ogunwobi OO (2010). Microsomal prostaglandin E synthase-1 inhibition blocks proliferation and enhances apoptosis in oesophageal adenocarcinoma cells without affecting endothelial prostacyclin production. Int J Cancer, 126, 2247-55.
  3. Bhutia SK, Dash R, Das SK, et al (2010). Mechanism of autophagy to apoptosis switch triggered in prostate cancer cells by antitumor cytokine melanoma differentiationassociated gene 7/interleukin-24. Cancer Res, 70, 3667-76. https://doi.org/10.1158/0008-5472.CAN-09-3647
  4. Cheng Y, Qiu F, Ye YC, et al (2009). Autophagy inhibits reactive oxygen species-mediated apoptosis via activating p38- nuclear factor-kappa B survival pathways in oridonin-treated murine fibrosarcoma L929 cells. FEBS J, 276, 1291-306. https://doi.org/10.1111/j.1742-4658.2008.06864.x
  5. Cheng Y, Wang M, Yu Y, et al (2006). Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function. J Clin Invest, 116, 1391-9. https://doi.org/10.1172/JCI27540
  6. Ciechomska IA, Goemans GC, Skepper JN, Tolkovsky AM (2009). Bcl-2 complexed with Beclin-1 maintains full antiapoptotic function. Oncogene, 28, 2128-41. https://doi.org/10.1038/onc.2009.60
  7. Chen N, Karantza-Wadsworth V (2009). Role and regulation of autophagy in cancer. Biochim Biophys Acta, 1793, 1516-23. https://doi.org/10.1016/j.bbamcr.2008.12.013
  8. Gao X, Zacharek A, Salkowski A, et al (1995). Loss of heterozygosity of the BRCA1 and other loci on chromosome 17q in human prostate cancer. Cancer Res, 55, 1002-5.
  9. Hanaka H, Pawelzik SC, Johnsen JI, et al (2009). Microsomal prostaglandin E synthase 1 determines tumor growth in vivo of prostate and lung cancer cells. Proc Natl Acad Sci U S A, 106, 18757-62. https://doi.org/10.1073/pnas.0910218106
  10. Hellerstedt BA, Pienta KJ (2002). The current state of hormonal therapy for prostate cancer. CA Cancer J Clin, 52, 154-79. https://doi.org/10.3322/canjclin.52.3.154
  11. Jakobsson PJ, Thoren S, Morgenstern R, Samuelsson B (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, 7220-5. https://doi.org/10.1073/pnas.96.13.7220
  12. Jain S, Chakraborty G, Raja R, Kale S, Kundu GC (2008). Prostaglandin E2 regulates tumor angiogenesis in prostate cancer. Cancer Res, 68, 7750-9. https://doi.org/10.1158/0008-5472.CAN-07-6689
  13. Jia RP, Xu LW, Su Q, et al (2008). Cyclooxygenase-2 expression is dependent upon epidermal growth factor receptor expression or activation in androgen independent prostate cancer. Asian J Androl, 10, 758-64. https://doi.org/10.1111/j.1745-7262.2008.00423.x
  14. Kawata R, Hyo S, Araki M, Takenaka H (2010). Expression of cyclooxygenase-2 and microsomal prostagalandin E synthase-1 in head and neck squamous cell carcinoma. Auris Nasus Larynx, 37, 482-7. https://doi.org/10.1016/j.anl.2009.11.009
  15. Lalier L, Cartron PF, Pedelaborde F, et al (2007). Increase in PGE2 biosynthesis induces a Bax dependent apoptosis correlated to patients' survival in glioblastoma multiforme. Oncogene, 26, 4999-5009. https://doi.org/10.1038/sj.onc.1210303
  16. Lau KM, LaSpina M, Long J, Ho SM (2000). Expression of estrogen receptor (ER)-alpha and ER-beta in normal and malignant prostatic epithelial cells: regulation by methylation and involvement in growth regulation. Cancer Res, 60, 3175-82.
  17. Lee LM, Pan CC, Cheng CJ, Chi CW, Liu TY (2001). Expression of cyclooxygenase-2 in prostate adenocarcinoma and benign prostatic hyperplasia. Anticancer Res, 21, 1291-4.
  18. Liang XH, Kleeman LK, Jiang HH, et al (1998). Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol, 72, 8586-96.
  19. Lian J, Karnak D, Xu L (2010). The Bcl-2-Beclin 1 interaction in (-)-gossypol-induced autophagy versus apoptosis in prostate cancer cells. Autophagy, 6, 1201-3. https://doi.org/10.4161/auto.6.8.13549
  20. Lian J, Wu X, He F, et al (2011). A natural BH3 mimetic induces autophagy in apoptosis-resistant prostate cancer via modulating Bcl-2-Beclin1 interaction at endoplasmic reticulum. Cell Death Differ, 18, 60-71. https://doi.org/10.1038/cdd.2010.74
  21. Liu B, Cheng Y, Zhang B, Bian HJ, Bao JK (2009). Polygonatum cyrtonema lectin induces apoptosis and autophagy in human melanoma A375 cells through a mitochondria-mediated ROS-p38-p53 pathway. Cancer Lett, 275, 54-60. https://doi.org/10.1016/j.canlet.2008.09.042
  22. Madaan S, Abel PD, Chaudhary KS, et al (2000). Cytoplasmic induction and over-expression of cyclooxygenase-2 in human prostate cancer: implications for prevention and treatment. BJU Int, 86, 736-41.
  23. Miracco C, Cosci E, Oliveri et al (2007). Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours. Int J Oncol, 30, 429-36.
  24. Myung SJ, Kim IH (2008). Role of prostaglandins in colon cancer. Korean J Gastroenterol, 51, 274-9.
  25. Murakami M, Naraba H, Tanioka T, et al (2000). Regulation of prostaglandin E2 biosynthesis by inducible membraneassociated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem, 275, 32783-92. https://doi.org/10.1074/jbc.M003505200
  26. Nakanishi M, Montrose DC, Clark P, et al (2008). Genetic deletion of mPGES-1 suppresses intestinal tumorigenesis. Cancer Res, 68, 3251-9. https://doi.org/10.1158/0008-5472.CAN-07-6100
  27. Nakanishi M, Gokhale V, Meuillet EJ, Rosenberg DW (2010). mPGES-1 as a target for cancer suppression:A comprehensive invited review "Phospholipase A2 and lipid mediators". Biochimie, 92, 660-4. https://doi.org/10.1016/j.biochi.2010.02.006
  28. Pattingre S, Levine B (2006). Bcl-2 inhibition of autophagy:a new route to cancer? Cancer Res, 66, 2885-8. https://doi.org/10.1158/0008-5472.CAN-05-4412
  29. Pecchi E, Dallaporta M, Jean A, Thirion S, Troadec JD (2008). mPGES-1 knock-out mice are resistant to cancer-induced anorexia despite the absence of central mPGES-1 upregulation in wild-type anorexic mice. J Neuroimmunol, 199, 104-14. https://doi.org/10.1016/j.jneuroim.2008.05.012
  30. Qu X, Yu J, Bhagat G, et al (2003). Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest, 112, 1809-20. https://doi.org/10.1172/JCI20039
  31. Rask K, Zhu Y, Wang W, Hedin L, Sundfeldt K (2006). Ovarian epithelial cancer:a role for PGE2-synthesis and signalling in malignant transformation and progression. Mol Cancer, 5, 62.
  32. Samuelsson B, Morgenstern R, Jakobsson PJ (2007). Membrane prostaglandin E synthase-1, a novel therapeutic target. Pharmacol Rev, 59, 207-24. https://doi.org/10.1124/pr.59.3.1
  33. Smith MR, Manola J, Kaufman DS, et al (2006). Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy. J Clin Oncol, 24, 2723-8. https://doi.org/10.1200/JCO.2005.03.7804
  34. Srivastava JK, Pandey M, Gupta S (2009). Chamomile, a novel and selective COX-2 inhibitor with anti-inflammatory activity. Life Sci, 85, 663-9. https://doi.org/10.1016/j.lfs.2009.09.007
  35. Takasu S, Tsukamoto T, Cao XY, et al (2008). Roles of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and beta-catenin activation in gastric carcinogenesis in N-methyl-N-nitrosourea-treated K19- C2mE transgenic mice. Cancer Sci, 99, 2356-64. https://doi.org/10.1111/j.1349-7006.2008.00983.x
  36. Wang M, Zukas AM, Hui Y, et al (2006). Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis. Proc Natl Acad Sci U S A, 103, 14507-12. https://doi.org/10.1073/pnas.0606586103
  37. Wingo PA, Cardinez CJ, Landis SH, et al (2003). Long-term trends in cancer mortality in the United States, 1930-1998. Cancer, 97, 3133-275. https://doi.org/10.1002/cncr.11380
  38. Wu D, Mennerich D, Arndt K, et al (2009). Comparison of microsomal prostaglandin E synthase-1 deletion and COX-2 inhibition in acute cardiac ischemia in mice. Prostaglandins Other Lipid Mediat, 90, 21-5. https://doi.org/10.1016/j.prostaglandins.2009.06.006

Cited by

  1. Prognostic Value of T Cell Immunoglobulin Mucin-3 in Prostate Cancer vol.14, pp.6, 2013, https://doi.org/10.7314/APJCP.2013.14.6.3897
  2. PGE2 signaling and its biosynthesis-related enzymes in cholangiocarcinoma progression vol.35, pp.8, 2014, https://doi.org/10.1007/s13277-014-2021-y
  3. Autophagy: Detection, regulation and its role in cancer and therapy response vol.90, pp.8, 2014, https://doi.org/10.3109/09553002.2014.907932
  4. mPGES-1 in prostate cancer controls stemness and amplifies epidermal growth factor receptor-driven oncogenicity vol.22, pp.4, 2015, https://doi.org/10.1530/ERC-15-0277
  5. Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers pp.1792-1082, 2015, https://doi.org/10.3892/ol.2015.2950