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High expression of Cdc25B and low expression of 14-3-3σ is associated with the development and poor prognosis in urothelial carcinoma of bladder

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Tumor Biology

Abstract

Cdc25 dual-specicity phosphatases are essential regulators at critical stages of cell cycle. Cdc25B is overexpressed in several human tumor types. The activity of Cdc25B is regulated by 14-3-3 dimer. To investigate the roles of Cdc25B and 14-3-3σ in bladder carcinoma, we examined expressions of Cdc25B and 14-3-3σ proteins in bladder carcinoma and cell lines and analyzed their roles in the development and prognosis of urinary bladder carcinoma. Immunohistochmistry was used to detect the expressions of Cdc25B and 14-3-3σ in 105 bladder carcinomas. Moreover, expressions of Cdc25B and 14-3-3σ were analyzed by real-time PCR and Western blot in 40 bladder carcinomas and 20 normal epithelial tissues. Specific siRNA was used to knockdown the expression of Cdc25B or 14-3-3σ. Wild-type plasmid was used to overexpress 14-3-3σ. MTT assay and Flow cytometry were used to examine proliferation and cell cycle of bladder cancer cells. There were higher Cdc25B expression and lower 14-3-3σ expression in carcinomas than in the adjacent normal tissues (P < 0.05), positive and negative correlations being noted with clinical stage and histopathologic grade. Cdc25B expression was positively correlated with recurrence and poor prognosis. Downregulation of Cdc25B resulted in slower growth, more G2/M cells and 14-3-3σ increasing. However, upregulation and downregulation of 14-3-3σ did not affect cell growth and Cdc25B expression. It showed that Cdc25B upregulation and 14-3-3σ downregulation might promote development of bladder cancer and suggested a poor prognosis. Moreover, Cdc25B could play an important role on the bladder cancer cell proliferation and cell cycle progression and regulate expression of 14-3-3σ.

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References

  1. Nakagawa T, Hara T, Kawahara T, et al. Prognostic risk stratification of patients with urothelial carcinoma of the bladder with recurrence after radical cystectomy. J Urol. 2013;189(4):1275–81.

    Article  PubMed  Google Scholar 

  2. Rodríguez Faba O, Palou J. Predictive factors for recurrence progression and cancer specific survival in high-risk bladder cancer. Curr Opin Urol. 2012;22(5):415–20.

    Article  PubMed  Google Scholar 

  3. Timofeev O, Cizmecioglu O, Settele F, Kempf T, Hoffmann I. Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at the G2/M transition. J Biol Chem. 2010;285(22):16978–90.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Sullivan C, Liu Y, Shen J, Curtis A, Newman C, et al. Novel interactions between FOXM1 and Cdc25A regulate the cell cycle. PLoS One. 2012;7(12):e51277.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Lau WS, Chen T, Wong YS. Allyl isothiocyanate induces G2/M arrest in human colorectal adenocarcinoma SW620 cells through down-regulation of Cdc25B and Cdc25C. Mol Med Rep. 2010;3(6):1023–30.

    PubMed  CAS  Google Scholar 

  6. Brunetto E, Ferrara AM, Rampoldi F, et al. Cdc25A protein stability represents a previously unrecognized target of HER2 signaling in human breast cancer: implication for a potential clinical relevance in trastuzumab treatment. Neoplasia. 2013;15(6):579–90.

    PubMed Central  PubMed  CAS  Google Scholar 

  7. Maiti GP, Mondal P, Mukherjee N, et al. Overexpression of EGFR in head and neck squamous cell carcinoma is associated with inactivation of SH3GL2 and Cdc25A genes. PLoS One. 2013;8(5):e63440.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Wu CF, Liu S, Lee YC, et al. RSK promotes G2/M transition through activating phosphorylation of Cdc25A and Cdc25B. Oncogene. 2013. doi:10.1038/onc.2013.182.

  9. Liu T, Yu X, Li G, et al. Rock2 regulates Cdc25A through ubiquitin proteasome system in hepatocellular carcinoma cells. Exp Cell Res. 2012;318(16):1994–2003.

    Article  PubMed  CAS  Google Scholar 

  10. Li N, Zhong X, Lin X, et al. Lin-28 homologue A (LIN28A) promotes cell cycle progression via regulation of cyclin-dependent kinase 2 (CDK2), cyclin D1 (CCND1), and cell division cycle 25 homolog A (Cdc25A) expression in cancer. J Biol Chem. 2012;287(21):17386–97.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. Ito Y, Yoshida H, Tomoda C, et al. Expression of cdc25B and cdc25A in medullary thyroid carcinoma: cdc25B expression level predicts a poor prognosis. Cancer Lett. 2005;229(2):291–7.

    Article  PubMed  CAS  Google Scholar 

  12. Aref S, Fouda M, El-Dosoky E, et al. c-Myc oncogene and Cdc25A cell activating phosphatase expression in non-Hodgkin’s lymphoma. Hematology. 2003;8(3):183–90.

    Article  PubMed  CAS  Google Scholar 

  13. Xing X, Chen J, Chen M. Expression of Cdc25 phosphatases in human gastric cancer. Dig Dis Sci. 2008;53(4):949–53.

    Article  PubMed  CAS  Google Scholar 

  14. Wu W, Slomovitz BM, Celestino J, Chung L, Thornton A, Lu KH. Coordinate expression of Cdc25B and ER-alpha is frequent in low-grade endometrioid endometrial carcinoma but uncommon in high-grade endometrioid and nonendometrioid carcinomas. Cancer Res. 2003;63(19):6195–9.

    PubMed  CAS  Google Scholar 

  15. Yu XY, Zhang Z, Liu J, Zhan B, Kong CZ. MicroRNA-141 is downregulated in human renal cell carcinoma and regulates cell survival by targeting Cdc25B. Onco Targets Ther. 2013;6:349–54.

    PubMed Central  PubMed  CAS  Google Scholar 

  16. Nakabayashi H, Hara M, Shimizu K. Prognostic significance of Cdc25B expression in gliomas. J Clin Pathol. 2006;59(7):725–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Broggini M, Buraggi G, Brenna A, et al. Cell cycle-related phosphatases Cdc25A and B expression correlates with survival in ovarian cancer patients. Anticancer Res. 2000;20(6C):4835–40.

    PubMed  CAS  Google Scholar 

  18. Lau KM, Chan QK, Pang JC, et al. Overexpression of HMGA1 deregulates tumor growth via cdc25A and alters migration/invasion through a cdc25A-independent pathway in medulloblastoma. Acta Neuropathol. 2012;123(4):553–71.

    Article  PubMed  CAS  Google Scholar 

  19. Peng CY, Graves PR, Thoma RS, Wu Z, Shaw AS, Piwnica-Worms H. Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science. 1997;277(5331):1501–5.

    Article  PubMed  CAS  Google Scholar 

  20. Giles N, Forrest A, Gabrielli B. 14-3-3 acts as an intramolecular bridge to regulate cdc25B localization and activity. J Biol Chem. 2003;278(31):28580–7.

    Article  PubMed  CAS  Google Scholar 

  21. Astuti P, Gabrielli B. Phosphorylation of Cdc25B3 Ser169 regulates 14-3-3 binding to Ser151 and Cdc25B activity. Cell Cycle. 2011;10(12):1960–7.

    Article  PubMed  CAS  Google Scholar 

  22. Astuti P, Boutros R, Ducommun B, Gabrielli B. Mitotic phosphorylation of Cdc25B Ser321 disrupts 14-3-3 binding to the high affinity Ser323 site. J Biol Chem. 2010;285(45):34364–70.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Mils V, Baldin V, Goubin F, et al. Specific interaction between 14-3-3 isoforms and the human Cdc25B phosphatase. Oncogene. 2000;19(10):1257–65.

    Article  PubMed  CAS  Google Scholar 

  24. Eble JN, Sauter G, Epstein JI. Pathology and genetics. Tumors of the urinary system and male genital organs. World Health Organization Classification of Tumors. Lyon: IARC Press; 2004.

    Google Scholar 

  25. Greene FL, Page DL, Fleming ID. AJCC cancer staging manual. 6th ed. New York: Springer; 2002.

    Book  Google Scholar 

  26. Zhang Z, Zhang G, Kong C. High expression of polo-like kinase 1 is associated with the metastasis and recurrence in urothelial carcinoma of bladder. Urol Oncol Semin Orig Investig. 2011; 31(7):1222–30

    Google Scholar 

  27. Boutros R, Mondesert O, Lorenzo C, et al. Cdc25B overexpression stabilises centrin 2 and promotes the formation of excess centriolar foci. PLoS One. 2013;8(7):e67822.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Yu XY, Zhang Z, Zhang GJ, Guo KF, Kong CZ. Knockdown of Cdc25B in renal cell carcinoma is associated with decreased malignant features. Asian Pac J Cancer Prev. 2012;13(3):931–5.

    Article  PubMed  Google Scholar 

  29. Wang Z, Trope CG, Flørenes VA, Suo Z, Nesland JM, Holm R. Overexpression of Cdc25B, Cdc25C and phospho-Cdc25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes. BMC Cancer. 2010;10:233.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  30. Yan X, Chua MS, He J, So SK. Small interfering RNA targeting Cdc25B inhibits liver tumor growth in vitro and in vivo. Mol Cancer. 2008;7:19.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by a Doctoral Fund from the Ministry of Education of China (20092104120007), Liaoning Provincial Natural Science Foundation (2013021066), Shenyang City Project of Key Laboratory (F13-293-1-00). The authors declare no competing financial interests.

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Authors and Affiliations

  1. Department of Urology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang City, Liaoning Province, People’s Republic of China, 110001

    Zhe Zhang & Chuize Kong

  2. Department of Hematology, Shengjing Hospital of China Medical University, Shenyang City, People’s Republic of China, 110022

    Guojun Zhang

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  1. Zhe Zhang
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  2. Guojun Zhang
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  3. Chuize Kong
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Correspondence to Chuize Kong.

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Zhang, Z., Zhang, G. & Kong, C. High expression of Cdc25B and low expression of 14-3-3σ is associated with the development and poor prognosis in urothelial carcinoma of bladder. Tumor Biol. 35, 2503–2512 (2014). https://doi.org/10.1007/s13277-013-1331-9

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  • DOI: https://doi.org/10.1007/s13277-013-1331-9

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