Asian Pacific Journal of Cancer Prevention

  • 제15권13호
  • /
  • Pages.5271-5276
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  • 2014
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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MEKK3 and Survivin Expression in Cervical Cancer: Association with Clinicopathological Factors and Prognosis

  • Cao, Xue-Quan (Department of Pathology, Taizhou Central Hospital of Taizhou Enze Medical Group) ;
  • Lu, Hong-Sheng (Department of Pathology, Taizhou Central Hospital of Taizhou Enze Medical Group) ;
  • Zhang, Ling (Department of Obstetrics and Gynecology, Taizhou Central Hospital of Taizhou Enze Medical Group) ;
  • Chen, Li-Li (Department of Pathology, Taizhou Central Hospital of Taizhou Enze Medical Group) ;
  • Gan, Mei-Fu (Department of Pathology, Taizhou Hospital of Taizhou Enze Medical Group)
  • 발행 : 2014.07.15
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초록

Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is an important protein kinase and a member of the MAPK family, which regulates cellular responses to environmental stress and serves as key integration points along the signal transduction cascade that not only link diverse extracellular stimuli to subsequent signaling molecules but also amplify the initiating signals to ultimately activate effector molecules and induce cell proliferation, differentiation and survival. To explore the relationship between MEKK3 and cell apoptosis, clinicopathology and prognosis, we characterize the expression of MEKK3 and survivin in cervical cancer. MEKK3 and survivin expression was measured by RT-PCR and Western blotting of fresh surgical resections from 30 cases of cervical cancer and 25 cases of chronic cervicitis. Protein expression was detected by tissue microarray and immunochemistry (En Vision) in 107 cases of cervical cancer, 86 cases of cervical intraepithelial neoplasia (CIN), and 35 cases of chronic cervicitis. Expression patterns were analyzed for their association with clinicopathological factors and prognosis in cervical cancer. Expression of MEKK3 and survivin mRNA was significantly higher in cervical cancer than in the controls (p<0.05). MEKK3 and survivin expression differed significantly between cervical carcinoma, CIN, and cervicitis (p<0.05) and correlated with clinical stage, infiltration depth, and lymph node metastasis (p<0.05). MEKK3 expression was positively correlated with survivin (p<0.05). Kaplan-Meier survival analysis showed that MEKK3 and survivin expression, lymph node metastasis, depth of invasion, and FIGO stage reduce cumulative survival. Cox multivariate regression analysis showed that MEKK3, survivin, and clinical staging are independent prognostic factors in cervical cancer (p<0.05). Expression of MEKK3 and survivin are significantly increased in cervical cancer, their overexpression participating in the occurrence and development of cervical cancer, with protein expression and clinical staging acting as independent prognostic factors for patients with cervical cancer.

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참고문헌

  1. Altieri DC (2003). Survivin in apoptosis control and cell cycle regulation in cancer. Prog Cell Cycle Res, 5, 447-52.
  2. Blank JL, Gerwins P, Johnson GL, et al (1996). Molecular cloning of mitogen-activated protein/EPK kinase kinase (MEKK)2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase. J Biol Chem, 271, 5361-8. https://doi.org/10.1074/jbc.271.10.5361
  3. Bongiovanni L, Romanucci M, Malatesta D, et al (2014). Survivin and related proteins in canine mammary tumors: immunohistochemical expression. Vet Pathol, 31. [Epub ahead of print]
  4. Cadron I, Van Gorp T, Amant F, et al (2007). Chemotherapy for recurrent cervical cancer. Gynecol Oncol, 107, 113-8. https://doi.org/10.1016/j.ygyno.2007.07.004
  5. Caffarel MM, Coleman N (2014). Oncostatin M receptor is a novel therapeutic target in cervical squamous cell carcinoma. J Pathol, 232, 386-90. https://doi.org/10.1002/path.4305
  6. Chang L, Karin M (2001). Mammalian MAP kinase signalling cascades. Nature, 410, 37-40. https://doi.org/10.1038/35065000
  7. Chen HA, Su CM, Hsieh HY, et al (2014). Clinical significance of survivin expression in patients with urothelial carcinoma. Dis Markers. 574985. [Epub 2014 Feb 5]
  8. Craig EA, Stevens MV, Vaillancourt RR, et al (2008). MAP3Ks as central regulators of cell fate during development.Developmental Dynamics, 237, 3102-14. https://doi.org/10.1002/dvdy.21750
  9. Deng Y, Yang J, McCarty M, et al (2007). MEKK3 is required for endothelium function but is not essential for tumor growth and angiogenesis. Am J Physiol Cell Physiol, 293, 1404-11. https://doi.org/10.1152/ajpcell.00058.2007
  10. Gao F, Zhang Y, Yang F, et al (2014). Survivin promotes the invasion of human colon carcinoma cells by regulating the expression of MMP 7. Mol Med Rep, 9, 825-30. https://doi.org/10.3892/mmr.2014.1897
  11. Gho GS, Ahn TS (2011). Expression of the surviving-2B splice variant related to the progression of colorectal carcinomas. J Korean Surg Soc, 80, 404-11. https://doi.org/10.4174/jkss.2011.80.6.404
  12. Hasan R, Sharma R, Saraya A, et al (2014). Mitogen activated protein kinase kinase kinase 3 (MAP3K3/MEKK3) overexpression is an early event in esophageal tumorigenesis and is a predictor of poor disease prognosis. BMC Cancer, 14, 2. https://doi.org/10.1186/1471-2407-14-2
  13. Indarti J, Aziz MF, Suryawati B, et al (2013). Scoring system and management algorithm assessing the role of survivin expression in predicting progressivity of HPV infections in precancerous cervical lesions. Asian Pac J Cancer Prev. 14, 1643-7. https://doi.org/10.7314/APJCP.2013.14.3.1643
  14. Johnson GL, Lapadat R (2002). Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 98, 1911-2.
  15. Karami H, Baradaran B, Esfahani A, et al (2013). siRNA-mediated silencing of survivin inhibits proliferation and enhances etoposide chemosensitivity in acute myeloid leukemia cells. Asian Pac J Cancer Prev, 14, 7719-24. https://doi.org/10.7314/APJCP.2013.14.12.7719
  16. Karimi ZM, Behtash N, Chiti Z, et al (2009). Cervical cancer and HPV vaccines in d eveloping coutries. Asian Pac J Cancer Prev, 10, 969-74.
  17. Kazuhiro N, Adam J, Kimple1, et al (2010). PB1 domain interaction of p62/Sequestosome1 and MEKK3regulates NF-${\kappa}B$ activation. J Biol Chem, 285, 2077-89. https://doi.org/10.1074/jbc.M109.065102
  18. Kitamura Hn in, Torigoe T, Honma I, et al (2006). Expression and antigenicity of Survivin, ahibitor of apoptosis family number, in bladder cancer: implication for specific immunotherapy. Urology, 67, 955-9. https://doi.org/10.1016/j.urology.2005.11.052
  19. Kumar A, Raziuddin M, Ralhan R, et al (2007). Discovery of deregulation of zinc homeostasis and its associated genes in esophageal squamous cell carcinoma usingicr cDNA m oarray. Int J Cancer, 120, 230-42. https://doi.org/10.1002/ijc.22246
  20. LaCasse EC, Mahoney DJ, Cheung HH, et al (2008). IAP-targeted therapies for cancer. Oncogene, 27, 6252-75. https://doi.org/10.1038/onc.2008.302
  21. Li F, Ambrosini G, Chu EY, et al (1998). Control of apoptosis and mitotic spindle checkpoint by survivin. Nature, 396, 580-4. https://doi.org/10.1038/25141
  22. Lu H, Gan M, Zhang G, et al (2010). Expression of survivin, caspase-3 and p53 in cervical cancer assessed by tissue microarray: correlation with clinicopathology and prognosis. Eur J Gynaecol Oncol, 31, 662-6.
  23. Samanta AK, Huang HJ, Le XF, et al (2009). MEKK3 expression correlates with nuclear factor kappa B activity and with expression of anti-apoptotic genes in serous ovarian carcinoma. Cancer, 115, 3897-908. https://doi.org/10.1002/cncr.24445
  24. Samanta AK, Huang HJ, Liao WS, et al (2004). Overexpression of MEKK3 confers resistance to apoptosis through activation of NF-KB. J Biol Chem, 279, 7576-83. https://doi.org/10.1074/jbc.M311659200
  25. Srivastava K, Srivastava A, Mittal B (2012). Survivin promoter .31G/C (rs9904341) polymorphism and cancer susceptibility: a meta-analysis. Molecular Biology Reports, 39, 1509-16. https://doi.org/10.1007/s11033-011-0889-9
  26. Sun WJ, Li HX, YU Y, et al (2009). MEKK3 is required for lysophosphatidic acid-induced NF-${\kappa}B$ activation.Cell Signal, 21, 1488-94. https://doi.org/10.1016/j.cellsig.2009.05.007
  27. Wand H, Xi X, Kong X, et al (2004). The expression and significance of Survivin mRNA in urinary bladder carcinomas. J Cancer Res Clin Oncol, 130, 487-90.
  28. Wu SF, Zhang JW, Qian WY, et al (2012). Altered expression of survivin, Fas and FasL contributed to cervical cancer development and metastasis. Eur Rev Med Pharmacol Sci, 16, 2044-50.
  29. Xu BE, Stippec S, Lenertz L, et al (2004). WNK1 activates ERK5 by an MEKK2/3-dependent mechanism. J Biol Chem, 279, 7826-31. https://doi.org/10.1074/jbc.M313465200
  30. Yang J, Lin Y, Guo Z, et al (2001). The essential role of MEKK3 in TNF-induced NF-${\kappa}B$ activation. Nat Immunol, 2, 620-4. https://doi.org/10.1038/89769
  31. YU L, Wang X, Langley RR, et al (2006). The role of MEKK3 in osteosarcoma invasion and metastasis. Proc Amer Assoc Cancer Res, 47, 207-10.

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  3. Expression and Prognostic Role of MEKK3 and pERK in Patients with Renal Clear Cell Carcinoma vol.16, pp.6, 2015, https://doi.org/10.7314/APJCP.2015.16.6.2495
  4. Survivin Overexpression Is Associated with Aggressive Clinicopathological Features in Cervical Carcinoma: A Meta-Analysis vol.11, pp.10, 2016, https://doi.org/10.1371/journal.pone.0165117
  5. A panel of autoantibodies as potential early diagnostic serum biomarkers in patients with cervical cancer vol.37, pp.7, 2016, https://doi.org/10.1007/s13277-015-4472-1
  6. Clinicopathological significance of survivin expression in patients with cervical cancer: A systematic meta-analysis vol.8, pp.5, 2017, https://doi.org/10.1080/21655979.2016.1252879
  7. Novel Somatic Copy Number Alteration Identified for Cervical Cancer in the Mexican American Population vol.4, pp.3, 2016, https://doi.org/10.3390/medsci4030012