TPX2 Overexpression in Medullary Thyroid Carcinoma Mediates TT Cell Proliferation
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  • 作者:Xiaolin Yang (1)
    Geling Liu (1)
    Hongzhen Xiao (1)
    Fang Yu (1)
    Xiuxiu Xiang (1)
    Yifang Lu (1)
    Weijuan Li (1)
    Xiuling Liu (1)
    Sha Li (1)
    Yanping Shi (1)
  • 关键词:Medullary thyroid cancer ; TPX2 ; siRNA ; Proliferation ; Apoptosis
  • 刊名:Pathology & Oncology Research
  • 出版年:2014
  • 出版时间:July 2014
  • 年:2014
  • 卷:20
  • 期:3
  • 页码:641-648
  • 全文大小:
  • 参考文献:1. Simard EP, Ward EM, Siegel R, Jemal A (2012) Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin 62(2):118-28
    2. Trimboli P, Ulisse S, Graziano F, Marzullo A, Ruggieri M, Calvanese A, Piccirilli F, Cavaliere R, Fumarola A, D’Armiento M (2006) Trend in thyroid carcinoma size, age at diagnosis, and histology in a retrospective study of 500 cases diagnosed over 20 years. Thyroid 16(11):1151-155 CrossRef
    3. Rahmani N, Abbas Hashemi S, Fazli M, Raisian M (2013) Clinical management and outcomes of papillary, follicular and medullary thyroid cancer surgery. Med Glas (Zenica) 10(1):164-67
    4. Janssen A, Medema RH (2012) Genetic instability: tipping the balance. Oncogene. doi:10.1038/onc.2012.576
    5. Lin D, Ma Y, Xiao T, Guo S, Han N, Su K, Yi S, Fang J, Cheng S, Gao Y (2006) TPX2 expression and its significance in squamous cell carcinoma of lung. Zhonghua Bing Li Xue Za Zhi Chin J Pathol 35(9):540
    6. Shigeishi H, Ohta K, Hiraoka M, Fujimoto S, Minami M, Higashikawa K, Kamata N (2009) Expression of TPX2 in salivary gland carcinomas. Oncol Rep 21(2):341
    7. Mohsenifar J, Almassi-Aghdam M, Mohammad-Taheri Z, Zare K, Jafari B, Atri M, Mortazavi S-H, Azadeh P, Bagherzadeh M, Rahimi F (2007) Prognostic values of proliferative markers ki-67 and repp86 in breast cancer. Arch Iran Med 10(1):27-1
    8. Baldini E, Arlot-Bonnemains Y, Sorrenti S, Mian C, Pelizzo MR, De Antoni E, Palermo S, Morrone S, Barollo S, Nesca A, Moretti CG, D’Armiento M, Ulisse S (2011) Aurora kinases are expressed in medullary thyroid carcinoma (MTC) and their inhibition suppresses in vitro growth and tumorigenicity of the MTC derived cell line TT. BMC Cancer 11:411 CrossRef
    9. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3(6):1101-108 CrossRef
    10. Wittmann T, Hyman A, Desai A (2001) The spindle: a dynamic assembly of microtubules and motors. Nat Cell Biol 3:E28–E34 CrossRef
    11. Aguirre-Portolés C, Bird AW, Hyman A et al (2012) TPX2 controls spindle integrity, genome stability, and tumor development. Cancer Res 72(6):1518-528 CrossRef
    12. Warner SL, Stephens BJ, Nwokenkwo S, Hostetter G, Sugeng A, Hidalgo M, Trent JM, Han H, Von Hoff DD (2009) Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells. Clin Cancer Res 15(21):6519-528 CrossRef
    13. Tonon G, Wong K-K, Maulik G, Brennan C, Feng B, Zhang Y, Khatry DB, Protopopov A, You MJ, Aguirre AJ (2005) High-resolution genomic profiles of human lung cancer. Proc Natl Acad Sci U S A 102(27):9625-630 CrossRef
    14. Sillars-Hardebol AH, Carvalho B, Tijssen M, Belien JA, de Wit M, Delis-van Diemen PM, Ponten F, van de Wiel MA, Fijneman RJ, Meijer GA (2012) TPX2 and AURKA promote 20q amplicon-driven colorectal adenoma to carcinoma progression. Gut 61(11):1568-575 CrossRef
    15. Chang H, Wang J, Tian Y, Xu J, Gou X, Cheng J (2012) The TPX2 gene is a promising diagnostic and therapeutic target for cervical cancer. Oncol Rep 27(5):1353-359
    16. Li B, Qi XQ, Chen X, Huang X, Liu GY, Chen HR, Huang CG, Luo C, Lu YC (2010) Expression of targeting protein for Xenopus kinesin-like protein 2 is associated with progression of human malignant astrocytoma. Brain Res 1352:200-07 CrossRef
    17. Morgan-Lappe SE, Tucker LA, Huang X, Zhang Q, Sarthy AV, Zakula D, Vernetti L, Schurdak M, Wang J, Fesik SW (2007) Identification of Ras-related nuclear protein, targeting protein for xenopus kinesin-like protein 2, and stearoyl-CoA desaturase 1 as promising cancer targets from an RNAi-based screen. Cancer research 67(9):4390-398 CrossRef
    18. Carson DA, Lois A (1995) Cancer progression and p53. Lancet 346(8981):1009-011 CrossRef
    19. Pascreau G, Eckerdt F, Lewellyn AL, Prigent C, Maller JL (2009) Phosphorylation of p53 is regulated by TPX2-Aurora A in xenopus oocytes. J Biol Chem 284(9):5497-505 CrossRef
    20. Marumoto T, Zhang D, Saya H (2005) Aurora-A—a guardian of poles. Nat Rev Cancer 5(1):42-0 CrossRef
    21. Ferchichi I, Sassi Hannachi S, Baccar A et al (2013) Assessment of Aurora A kinase expression in breast cancer: A tool for early diagnosis? Dis Markers 34(2):63-9
    22. Lee ECY, Frolov A, Li R, Ayala G, Greenberg NM (2006) Targeting Aurora kinases for the treatment of prostate cancer. Cancer research 66(10):4996-002 CrossRef
    23. Ulisse S, Delcros JG, Baldini E, Toller M, Curcio F, Giacomelli L, Prigent C, Ambesi-Impiombato FS, D’Armiento M, Arlot-Bonnemains Y (2006) Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues. Int J Cancer 119(2):275-82
    24. Kufer TA, Silljé HH, K?rner R, Gruss OJ, Meraldi P, Nigg EA (2002) Human TPX2 is required for targeting Aurora-A kinase to the spindle. J Cell Biol 158(4):617-23
    25. Bayliss R, Sardon T, Ebert J, Lindner D, Vernos I, Conti E (2004) Determinants for Aurora-A activation and Aurora-B discrimination by TPX2. Cell Cycle 3(4):402-05
    26. Eyers PA, Erikson E, Chen LG, Maller JL (2003) A novel mechanism for activation of the protein kinase Aurora A. Curr Biol CB 13(8):691 CrossRef
    27. Katayama H, Sasai K, Kawai H, Yuan Z-M, Bondaruk J, Suzuki F, Fujii S, Arlinghaus RB, Czerniak BA, Sen S (2003) Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 36(1):55-2
    28. Liu Q, Kaneko S, Yang L, Feldman RI, Nicosia SV, Chen J, Cheng JQ (2004) Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. J Biol Chem 279(50):52175-2182 CrossRef
    29. Rieder CL (2011) Mitosis in vertebrates: the G2/M and M/A transitions and their associated checkpoints. Chromosom Res 19(3):291-06 CrossRef
    30. Sasayama T, Marumoto T, Kunitoku N, Zhang D, Tamaki N, Kohmura E, Saya H, Hirota T (2005) Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1. Genes Cells 10(7):627-38 CrossRef
    31. Marumoto T, Hirota T, Morisaki T, Kunitoku N, Zhang D, Ichikawa Y, Sasayama T, Kuninaka S, Mimori T, Tamaki N (2002) Roles of aurora‐A kinase in mitotic entry and G2 checkpoint in mammalian cells. Genes Cells 7(11):1173-182 CrossRef
    32. Moore JD (2013) In the wrong place at the wrong time: does cyclin mislocalization drive oncogenic transformation? Nat Rev Cancer 13(3):201-08 CrossRef
  • 作者单位:Xiaolin Yang (1)
    Geling Liu (1)
    Hongzhen Xiao (1)
    Fang Yu (1)
    Xiuxiu Xiang (1)
    Yifang Lu (1)
    Weijuan Li (1)
    Xiuling Liu (1)
    Sha Li (1)
    Yanping Shi (1)

    1. Department of Endocrinology (Section I), Tangshan Workers Hospital, Tangshan, China
  • ISSN:1532-2807
文摘
TPX2 (targeting protein for xenopus kinesin-like protein 2), a microtubule-associated protein, plays an important role in the formation of the mitotic spindle. Abnormal expression of TPX2 in various types of malignant tumors has been reported, but less is known for medullary thyroid cancer (MTC). We investigated the expression of TPX2 in human MTC tissues and its potential use as a therapeutic target. Immunohistochemical analysis of TPX2 expression was performed for 32 cases of MTC and 8 cases of normal thyroid. TPX2 expression was found to be significantly higher in MTC compared to normal thyroid tissues (P-lt;-.05), and to be associated with tumor size, lymph node metastasis, and advanced disease stage. The cellular effects of TPX2 knockdown, including cell proliferation, apoptosis, cell cycle diffusions, and mitotic gene expression were investigated using small interfering RNA (siRNA). TPX2-siRNA caused G1 and G2-phase cell cycle arrest, inhibited cell proliferation, and induced apoptosis. TPX2-siRNA also downregulated Aurora-A and cyclinB1 protein expression in MTC cells and enhanced the expression of p53 protein (P-lt;-.05). These results suggest that TPX2 may be of potential use as a new marker for MTC prognosis and therapy.

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