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Expression and Significance of the Wip1 Proto-oncogene in Colorectal Cancer

  • Li, Zong-Tao (Department of Surgery, Hebei Medical University) ;
  • Zhang, Liu (Department of Surgery, Hebei Medical University) ;
  • Gao, Xiao-Zeng (Department of Surgery, Hebei Medical University) ;
  • Jiang, Xiao-Hua (Department of Surgery, Hebei Medical University) ;
  • Sun, Li-Qian (Department of Surgery, Hebei Medical University)
  • Published : 2013.03.30

Abstract

Aim: To investigate the level of expression of proto-oncogene Wip1 and its physiological significance in colorectal cancer. Methods: Immunohistochemistry, semi-quantitative RT-PCR, and Western blotting were used to analyze Wip1 mRNA and protein expression in 120 cases of colorectal cancer and normal tissues to study relationships with clinical symptoms and disease prognosis. Results: The level of Wip1 protein expression was found to be significantly higher in colorectal cancer tissues (85% (102/120)) than in normal tissues (30% (36/120)) (P<0.05). The relative amount of Wip1 protein in colorectal cancer tissue was also found to be significantly higher (P<0.05) than in normal tissues ($1.060{\pm}0.02$ and $0.640{\pm}0.023$, respectively). Semi-quantitative RT-PCR showed average Wip1 mRNA expression levels to be $1.113{\pm}0.018$ and $0.658{\pm}0.036$ for colorectal cancer tissue and adjacent normal tissue (P<0.05). The level of Wip1 protein expression was not correlated with age, gender, or tumor site, but appeared linked with lymph node metastasis, Dukes stage, histological grade, and liver metastasis. Individuals with high and low levels of Wip1 expression showed statistically significant differences in the five-year overall survival and recurrence-free survival rates (P<0.05). Conclusion: Wip1 mRNA and protein are highly expressed in colorectal cancers and may be associated with colorectal cancer development and progression.

References

  1. Aaron JS, Suet YL, Jane J, et al (2008). Micro RNA Expression Profiles Associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA, 299, 425-36. https://doi.org/10.1001/jama.299.4.425
  2. Bulavin DV, Demidov ON, Saito S, et al (2002). Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat Genet, 31, 210-5. https://doi.org/10.1038/ng894
  3. Castellino RC, De Bortoli M, Lu X, et al (2008). Medulloblastomas overexpress the p53-inactivating oncogene WIP1/PPM1D. J Neurooncol, 86, 245-56. https://doi.org/10.1007/s11060-007-9470-8
  4. Ding PR, Wan DS, Pan ZZ, et al (2006). Prognostic analysis of 384 male patients with rectal cancer. Cancer, 25, 1158-61.
  5. Doucette TA, Yang Y, Pedone C, et al (2012). WIP1 enhances tumor formation in a sonic hedgehog-dependent model of medulloblastoma. Neurosurgery, 70, 1002-10.
  6. Fiscella M, Zhang H, Fan S, et al (1997). Wip1, a novel human prote in phosphatase that is induced in response to ionizing radiation in a p53 - dependent manner. Proc Natl A cad Sci USA, 94, 6048-53. https://doi.org/10.1073/pnas.94.12.6048
  7. Fuku T, Semba S, Yutori H, Yokozaki H (2007). Increased wildtype p53 induced phosphatase1 (Wipl or PPM1D) expression correlated with downregulation of checkpoint kinase2 in human gastric carcinoma. Pathol Int, 57, 566-71. https://doi.org/10.1111/j.1440-1827.2007.02140.x
  8. Hayashi R, Tanoue K, Durell SR, et al (2011). Optimization of a cyclic peptide inhibitor of Ser/Thr phosphatase PPM1D (Wip1). Biochemistry, 50, 4537-49. https://doi.org/10.1021/bi101949t
  9. Hirasawa A, Saito-Ohara F, Inoue J, et a1 (2003). Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets. Clin Cancer Res, 10, 1995-2004.
  10. Hu W, Feng Z, Modica I, et al (2010). Gene amplifications in well-differentiated pancreatic neuroendocrine tumors inactivate the p53 pathway. Genes Cancer, 1, 360-8. https://doi.org/10.1177/1947601910371979
  11. Le Cuezennec X, Bulavin DV (2010). WIP1 phosphatase at the crossroads of cancer and aging. Trends Biochem Sci, 35, 109-14,. https://doi.org/10.1016/j.tibs.2009.09.005
  12. Liang C, Guo E, Lu S, et al (2012). Over-expression of wildtype p53-induced phosphatase 1 confers poor prognosis of patients with gliomas. Brain Res, 1444, 65-75,. https://doi.org/10.1016/j.brainres.2011.12.052
  13. Loukopoulos P, Shibata T, Katoh H, et a1 (2007). Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma, identification of genetic indicators that predict patient outcome. Cancer Sci, 98, 392-400. https://doi.org/10.1111/j.1349-7006.2007.00395.x
  14. Lu X, Bocangel D, Nannenga B, et al (2004). The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair. Mol Cell, 15, 621-34. https://doi.org/10.1016/j.molcel.2004.08.007
  15. Lu X, Nannenga B and Donehower LA (2005). PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev, 19, 1162-74. https://doi.org/10.1101/gad.1291305
  16. Park JY, Song JY, Kim HM, et al (2012). P53-Independent expression of wild-type p53-induced phosphatase 1 (Wip1) in methylmethane sulfonate-treated cancer cell lines and human tumors. Int J Biochem Cell Biol, 44, 896-904. https://doi.org/10.1016/j.biocel.2012.02.013
  17. Ren WM, Zhang YY, Luo JF (2012). The PPM1D expression and significance in papillary thyroid carcinoma. Pro Bed Experim Pathol, 28, 623-6.
  18. Saito OF, Imoto I, Inoue J, et al (2003). PPM1D is a potential target for 17q gain in neurob lastoma. Cancer Res, 63, 1876-83.
  19. Satoh N, Maniwa Y, Bermudez VP, et al (2011). Oncogenic phosphatase Wip1 is a novel prognostic marker for lung adenocarcinoma patient survival. Cancer Sci, 102, 1101-6. https://doi.org/10.1111/j.1349-7006.2011.01898.x
  20. Shreeram S, Demidov ON, Hee WK, et al (2006). Wip1 phosphatase modulates ATM-dependent signaling pathways. Mol Cell, 23, 754-64.
  21. Spinnler C, Hedstrom E, Li H, et al (2011). Abrogation of Wip1 expression by RITA-activated p53 potentiates apoptosis induction via activation of ATM and inhibition of HdmX. Cell Death Differ, 18, 1736-45. https://doi.org/10.1038/cdd.2011.45
  22. Wan D (2009). Epidemiologic trend of and strategies for colorectal cancer. Chin J Cancer, 9, 897-902.
  23. Wang P, Rao J, Yang H, Zhao H, Yang L (2011). Wip1 overexpression correlated with TP53/p14(ARF) pathway disruption in human astrocytomas. J Surg Oncol, 104, 679-84. https://doi.org/10.1002/jso.22004
  24. Yu E, Ahn YS, Jang SJ, et al (2007). Over expression of the wip1 gene abrogates the p38 MAPK/P53/Wip1 pathway and silences p16 expression in human breast cancers. Breast Cancer Res Treat, 101, 269-78. https://doi.org/10.1007/s10549-006-9304-y

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