Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Aberrant Expression of Pim-3 Promotes Proliferation and Migration of Ovarian Cancer Cells

  • Zhuang, Hao (Department of Medical Microbiology, School of Basic Medical Sciences, Department of Obstetrics &Gynecology, Tianjin Medical University) ;
  • Zhao, Man-Yin (Department of Obstetrics &Gynecology, Yantai City Zhifu district Maternal and Child health Hospital) ;
  • Hei, Kai-Wen (Department of Medical Microbiology, School of Basic Medical Sciences, Department of Obstetrics &Gynecology, Tianjin Medical University) ;
  • Yang, Bai-Cai (Department of Medical Microbiology, School of Basic Medical Sciences, Department of Obstetrics &Gynecology, Tianjin Medical University) ;
  • Sun, Li (Second Affiliated Hospital, Tianjin Medical University) ;
  • Du, Xue (General Hospital, Tianjin Medical University) ;
  • Li, Yong-Mei (Department of Medical Microbiology, School of Basic Medical Sciences, Department of Obstetrics &Gynecology, Tianjin Medical University)
  • Published : 2015.04.29
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Abstract

Pim kinase-3(Pim-3), a member of serine/threonine protein kinases, has been implicated in multiple human cancers and involved in Myc-induced tumorigenesis. However, little is known regarding its expression and biological function in human ovarian cancer. In this study we showed that the clinical significance and biological functions of Pim-3 in ovarian cancer and found that higher Pim-3 mRNA level are detected in ovarian cancer tissues than those in normal ovarian tissues. There are significant correlations between higher Pim-3 expression levels with the FIGO stage, histopathological subtypes, and distant metastasis in ovarian cancer patients. Lentivirus-mediated gene overexpression of Pim-3 significantly promotes the proliferation and migration of SKOV3 cell lines. Furthermore, MACC1 and Pim-3 expression were significantly correlated in human ovarian cancer cells, and overexpression of Pim-3 in ovary cancer cells increased MACC1 mRNA and protein expression. The data indicate that Pim-3 acts as a putative oncogene in ovary cancer and could be a viable diagnostic and therapeutic target for ovarian cancer.

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References

  1. Akue-Gedu R, Letribot B, Saugues E, et al (2012). Kinase inhibitory potencies and in vitro antiproliferative activities of N-10 substituted pyrrolo [2, 3-a]carbazole derivatives. Bioorg Med Chem Lett, 22, 3807-9. https://doi.org/10.1016/j.bmcl.2012.03.098
  2. Behan JW, Yun JP, Proektor MP, et al (2009). Adipocytes impair leukemia treatment in mice. Cancer Res, 69, 7867-74. https://doi.org/10.1158/0008-5472.CAN-09-0800
  3. Chen J, Kobayashi M, Darmanin S, et al (2009). Pim-1 plays a pivotal role in hypoxia-induced chemoresistance. Oncogene, 28, 2581-92. https://doi.org/10.1038/onc.2009.124
  4. Dave SS, Fu K, Wright GW, et al (2006). Molecular diagnosis of Burkitt's lymphoma. N Engl J Med, 354, 2431-42. https://doi.org/10.1056/NEJMoa055759
  5. Deneen B, Welford SM, Ho T, et al (2003). PIM3 proto-oncogene kinase is a common transcriptional target of divergent EWS/ETS oncoproteins. Mol Cell Biol, 23, 3897-908. https://doi.org/10.1128/MCB.23.11.3897-3908.2003
  6. Feldman JD, Vician L, Crispino M, et al (1998). KID-1, a protein kinase induced by depolarization in brain. J Biol Chem, 273, 16535-43. https://doi.org/10.1074/jbc.273.26.16535
  7. Forshell LP, Li Y, Forshell TZ, et al (2011). The direct Myc target Pim3 cooperates with other Pim kinases in supporting viability of Myc-induced B-cell lymphomas. Oncotarget, 2, 448-60. https://doi.org/10.18632/oncotarget.283
  8. Fujii C, Nakamoto Y, Lu P, et al (2005). Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines. Int J Cancer, 114, 209-18. https://doi.org/10.1002/ijc.20719
  9. Galimi F, Torti D, Sassi F, et al (2011). Genetic and expression analysis of MET, MACC1, and HGF in metastatic colorectal cancer: response to met inhibition in patient xenografts and pathologic correlations. Clin Cancer Res, 17, 3146-56. https://doi.org/10.1158/1078-0432.CCR-10-3377
  10. Gavara L, Suchaud V, Nauton L, et al (2013). Identification of pyrrolo[2, 3-g]indazoles as new Pim kinase inhibitors. Bioorg Med Chem Lett, 23, 2298-301. https://doi.org/10.1016/j.bmcl.2013.02.074
  11. Konietzko U, Kauselmann G, Scafidi J, et al (1999). Pim kinase expression is induced by LTP stimulation and required for the consolidation of enduring LTP. EMBO J, 18, 3359-69. https://doi.org/10.1093/emboj/18.12.3359
  12. Li YY, Popivanova BK, Nagai Y, et al (2006). Pim-3, a protooncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block bad-mediated apoptosis in human pancreatic cancer cell lines. Cancer Res, 66, 6741-7. https://doi.org/10.1158/0008-5472.CAN-05-4272
  13. Li YY, Wang YY, Taniguchi T, et al (2010). Identification of stemonamide synthetic intermediates as a novel potent anticancer drug with an apoptosis-inducing ability. Int J Cancer, 127, 474-84.
  14. Li YY, Wu Y, Tsuneyama K, et al (2009). Essential contribution of Ets-1 to constitutive Pim-3 expression in human pancreatic cancer cells. Cancer Sci, 100, 396-404. https://doi.org/10.1111/j.1349-7006.2008.01059.x
  15. Lou L, Wang Y, Cui J, et al (2014). Differential expression of Pim-3, c-Myc, and p-p27 proteins in adenocarcinomas of the gastric cardia and distal stomach. Tumour Biol, 35, 5029-36. https://doi.org/10.1007/s13277-014-1664-z
  16. Migliore C, Martin V, Leoni VP, et al (2012). MiR-1 downregulation cooperates with MACC1 in promoting MET overexpression in human colon cancer. Clin Cancer Res, 18, 737-47. https://doi.org/10.1158/1078-0432.CCR-11-1699
  17. Mikkers H, Nawijn M, Allen J, et al (2004). Mice deficient for all PIM kinases display reduced body size and impaired responses to hematopoietic growth factors. Mol Cell Biol, 24, 6104-15. https://doi.org/10.1128/MCB.24.13.6104-6115.2004
  18. Mukaida N, Wang YY, Li YY (2011). Roles of Pim-3, a novel survival kinase, in tumorigenesis. Cancer Sci, 102, 1437-42. https://doi.org/10.1111/j.1349-7006.2011.01966.x
  19. Mumenthaler SM, Ng PY, Hodge A, et al (2009). Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther, 8, 2882-93. https://doi.org/10.1158/1535-7163.MCT-09-0293
  20. Nakano H, Saito N, Parker L, et al (2012). Rational evolution of a novel type of potent and selective proviral integration site in Moloney murine leukemia virus kinase 1 (PIM1) inhibitor from a screening-hit compound. J Med Chem, 55, 5151-64. https://doi.org/10.1021/jm3001289
  21. Narlik-Grassow M, Blanco-Aparicio C, Cecilia Y, et al (2012). The essential role of PIM kinases in sarcoma growth and bone invasion. Carcinogenesis, 33, 1479-86. https://doi.org/10.1093/carcin/bgs176
  22. Peltola K, Hollmen M, Maula SM, et al (2009). Pim-1 kinase expression predicts radiation response in squamocellular carcinoma of head and neck and is under the control of epidermal growth factor receptor. Neoplasia, 11, 629-36. https://doi.org/10.1593/neo.81038
  23. Popivanova BK, Li YY, Zheng H, et al (2007). Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Badmediated apoptosis. Cancer Sci, 98, 321-8. https://doi.org/10.1111/j.1349-7006.2007.00390.x
  24. Rossi D, Berra E, Cerri M, et al (2006). Aberrant somatic hypermutation in transformation of follicular lymphoma and chronic lymphocytic leukemia to diffuse large B-cell lymphoma. Haematologica, 91, 1405-9.
  25. Shimokawa H, Uramoto H, Onitsuka T, et al (2011). Overexpression of MACC1 mRNA in lung adenocarcinoma is associated with postoperative recurrence. J Thorac Cardiovasc Surg, 141, 895-8. https://doi.org/10.1016/j.jtcvs.2010.09.044
  26. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  27. Stein U (2013). MACC1 - a novel target for solid cancers. Expert Opin Ther Targets, 17, 1039-52. https://doi.org/10.1517/14728222.2013.815727
  28. Stein U, Burock S, Herrmann P, et al (2012). Circulating MACC1 transcripts in colorectal cancer patient plasma predict metastasis and prognosis. PLoS One, 7, 49249. https://doi.org/10.1371/journal.pone.0049249
  29. Stein U, Walther W, Arlt F, et al (2009). MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis. Nat Med, 15, 59-67. https://doi.org/10.1038/nm.1889
  30. Wang J, Lao L, Zhao H, et al (2014). Serine threonine kinase Pim-3 regulates STAT3 pathway to inhibit proliferation of human liver cancers. Int J Clin Exp Med, 7, 348-55.
  31. Wang Z, Li XM, Shang K, et al (2013). T-18, a stemonamide synthetic intermediate inhibits Pim kinase activity and induces cell apoptosis, acting as a potent anticancer drug. Oncol Rep, 29, 1245-51.
  32. Warnecke-Eberz U, Bollschweiler E, Drebber U, et al (2009). Prognostic impact of protein overexpression of the protooncogene PIM-1 in gastric cancer. Anticancer Res, 29, 4451-5.
  33. Wright G, Tan B, Rosenwald A, et al (2003). A gene expressionbased method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci USA, 100, 9991-6. https://doi.org/10.1073/pnas.1732008100
  34. Yang H, Wang Y, Qian H, et al (2011). Pim protein kinase-3 is regulated by TNF-alpha and promotes endothelial cell sprouting. Mol Cells, 32, 235-41. https://doi.org/10.1007/s10059-011-1026-z
  35. Zemskova M, Sahakian E, Bashkirova S, et al (2008). The PIM1 kinase is a critical component of a survival pathway activated by docetaxel and promotes survival of docetaxel-treated prostate cancer cells. J Biol Chem, 283, 20635-44. https://doi.org/10.1074/jbc.M709479200
  36. Zhang F, Liu B, Wang Z, et al (2013). A novel regulatory mechanism of Pim-3 kinase stability and its involvement in pancreatic cancer progression. Mol Cancer Res, 11, 1508-20. https://doi.org/10.1158/1541-7786.MCR-13-0389
  37. Zhang P, Wang H, Min X, et al (2009). Pim-3 is expressed in endothelial cells and promotes vascular tube formation. J Cell Physiol, 220, 82-90. https://doi.org/10.1002/jcp.21733
  38. Zhang R, Shi H, Chen Z, et al (2011). Effects of metastasisassociated in colon cancer 1 inhibition by small hairpin RNA on ovarian carcinoma OVCAR-3 cells. J Exp Clin Cancer Res, 30, 83. https://doi.org/10.1186/1756-9966-30-83
  39. Zhang RT, Ren F, Shi HR (2014). Expression of metastasisassociated in colon cancer-1 in different stages of epithelial ovarian cancer. Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 36, 47-51. (in Chinese)
  40. Zheng HC, Tsuneyama K, Takahashi H, et al (2008). Aberrant Pim-3 expression is involved in gastric adenomaadenocarcinoma sequence and cancer progression. J Cancer Res Clin Oncol, 134, 481-8. https://doi.org/10.1007/s00432-007-0310-1

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