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Tumor Biology
Published in: Tumor Biology 1/2016

01-01-2016 | Original Article

A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage

Authors: Mariana F. Gayyed, Nehad M. R. Abd El-Maqsoud, Ehab Rifat Tawfiek, Saad Abdelnaby A. El Gelany, Mohamed Fathy Abdel Rahman

Published in: Tumor Biology | Issue 1/2016

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Abstract

High expression of cell division cycle 20 homolog (CDC20), a key component of the spindle assembly checkpoint (SAC), has been reported in various malignancies and plays a vital role in tumorigenesis and progression. The goal of this study was to evaluate the utility of CDC20 immunostaining in a wide range of malignant tumors. CDC20 immunohistochemistry was evaluated in normal tissues and compared to the most frequently occurring malignant tumors in these tissues (bladder, breast, cervical, colonic, endometrial, gastric, head and neck, liver, lung, ovarian, pancreatic, prostatic, renal, thyroid carcinomas, and testicular seminoma). Normal/non-neoplastic tissues showed positive CDC20 expression in 19.44 % of all examined cases. CDC20 staining was negative in normal and non-neoplastic tissues from the bladder, cervix, liver, stomach, and thyroid. From the all malignant tumors examined 55.7 % showed high CDC20 expression while low expression was found in 44.3 %. High expression of CDC20 was associated with high tumor grade in the bladder (p = 0.027), cervical (p = 0.032), colonic (p = 0.026), endometrial (p = 0.016), gastric (p = 0.033), liver (p = 0.028), ovarian (p = 0.044), prostatic (p = 0.040), and renal (p = 0.048) carcinomas. There was a significant correlation between high CDC20 expression and advanced tumor stage in carcinoma of the breast, colon, endometrium, and prostate (p = 0.021, p = 0.040, p = 0.047, p = 0.031, respectively). CDC20 expression may be useful as a biomarker of tumor prognosis and as a therapeutic target of human cancer.
Literature
1.
Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 1998;396(6712):643–9.CrossRefPubMed
2.
Suijkerbuijk SJ, Kops GJ. Preventing aneuploidy: the contribution of mitotic checkpoint proteins. Biochim Biophys Acta. 2008;1786(1):24–31.PubMed
3.
4.
Jallepalli PV, Lengauer C. Chromosome segregation and cancer: cutting through the mystery. Nat Rev Cancer. 2001;1(2):109–17.CrossRefPubMed
5.
6.
Bharadwaj R, Yu H. The spindle checkpoint, aneuploidy, and cancer. Oncogene. 2004;23(11):2016–27.CrossRefPubMed
7.
Li Y, Benezra R. Identification of a human mitotic checkpoint gene: hsMAD2. Science. 1996;274(5285):246–8.CrossRefPubMed
8.
9.
Iwanaga Y, Kasai T, Kibler K, Jeang KT. Characterization of regions in hsMAD1 needed for binding hsMAD2. A polymorphic change in an hsMAD1 leucine zipper affects MAD1–MAD2 interaction and spindle checkpoint function. J Biol Chem. 2002;277(34):31005–13.CrossRefPubMed
10.
11.
Haruki N, Saito H, Harano T, Nomoto S, Takahashi T, Osada H, et al. Molecular analysis of the mitotic checkpoint genes BUB1, BUBR1 and BUB3 in human lung cancers. Cancer Lett. 2001;16292:201–5.CrossRef
12.
Hernando E, Orlow I, Liberal V, Nohales G, Benezra R, CordonCardo C. Molecular analyses of the mitotic checkpoint components hsMAD2, hBUB1 and hBUB3 in human cancer. Int J Cancer. 2001;95(4):223–7.CrossRefPubMed
13.
Ouyang B, Knauf JA, Ain K, Nacev B, Fagin JA. Mechanisms of aneuploidy in thyroid cancer cell lines and tissues:evidence for mitotic checkpoint dysfunction without mutations in BUB1 and BUBR1. Clin Endocrinol (Oxf). 2002;56(3):341–50.CrossRef
14.
Doak SH, Jenkins GJ, Parry EM, Griffiths AP, Baxter JN, Parry JM. Differential expression of the MAD2, BUB1 and HSP27 genes in Barrett’s oesophagus—their association with aneuploidy and neoplastic progression. Mutat Res. 2004;547(1–2):133–44.CrossRefPubMed
15.
Jeong SJ, Shin HJ, Kim SJ, Ha GH, Cho BI, Baek KH, et al. Transcriptional abnormality of the hsMAD2 mitotic checkpoint gene is a potential link to hepatocellular carcinogenesis. Cancer Res. 2004;64(23):8666–73.CrossRefPubMed
16.
Sze KM, Ching YP, Jin DY, Ng IO. Association of MAD2 expression with mitotic checkpoint competence in hepatoma cells. J Biomed Sci. 2004;11(6):920–7.CrossRefPubMed
17.
Kienitz A, Vogel C, Morales I, Muller R, Bastians H. Partial downregulation of MAD1 causes spindle checkpoint inactivation and aneuploidy, but does not confer resistance towards taxol. Oncogene. 2004;24(26):4301–10.CrossRef
18.
Wasch R, Engelbert D. Anaphase-promoting complex dependent proteolysis of cell cycle regulators and genomic instability of cancer cells. Oncogene. 2005;24(1):1–10.CrossRefPubMed
19.
Musacchio A, Salmon ED. The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol. 2007;8(5):379–93.CrossRefPubMed
20.
21.
Sudakin V, Chan GK, Yen TJ. Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. J Cell Biol. 2001;154(5):925–36.CrossRefPubMedPubMedCentral
22.
Howell BJ, Moree B, Farrar EM, Stewart S, Fang G, Salmon ED. Spindle checkpoint protein dynamics at kinetochores in living cells. Curr Biol. 2004;14(11):953–64.CrossRefPubMed
23.
Chang DZ, Ma Y, Ji B, Liu Y, Hwu P, Abbruzzese JL, et al. Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression. J Hematol Oncol. 2012;4:5–15.CrossRef
24.
Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kaji M. Overexpression of CDC20 predicts poor prognosis in primary non small cell lung cancer patients. J Surg Oncol. 2012;106(4):423–30.CrossRefPubMed
25.
Choi JW, Kim Y, Lee JH, Kim YS. High expression of spindle assembly checkpoint proteins CDC20 and MAD2 is associated with poor prognosis in urothelial bladder cancer. Virchows Arch. 2013;463(5):681–7.CrossRefPubMed
26.
Wu WJ, Hu KS, Wang DS, Zeng ZL, Zhang DS, Chen DL, et al. CDC20 overexpression predicts a poor prognosis for patients with colorectal cancer. J Transl Med. 2013;11:142.CrossRefPubMedPubMedCentral
27.
Moura IM, Delgado ML, Silva PM, Lopes CA, do Amaral JB, Monteiro LS. High CDC20 expression is associated with poor prognosis in oral squamous cell carcinoma. J Oral Pathol Med. 2014;43(3):225–31.CrossRefPubMed
28.
Izawa D, Pines J. The mitotic checkpoint complex binds a second CDC20 to inhibit activate APC/C. Nature. 2015;517(7536):631–4.CrossRefPubMed
29.
Hongtao Y. Cdc20. A WD40 activator for a cell cycle degradation machine. Mol Cell. 2007;27(1):3–16.CrossRef
30.
Mondal G, Sengupta S, Panda CK, Gollin SM, Saunders WS, Roychoudhury S. Overexpression of CDC20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. Carcinogenesis. 2007;28(1):81–92.CrossRefPubMed
31.
Clarke DJ, Segal M, Andrews CA, Rudyak SG, Jensen S, Smith K, et al. S-phase checkpoint controls mitosis via an APC-independent CDC20p function. Nat Cell Biol. 2003;5(10):928–35.CrossRefPubMed
32.
Shi J, Orth JD, Mitchison T. Cell type variation in responses to antimitotic drugs that target microtubules and kinesin-5. Cancer Res. 2008;68(9):3269–76.CrossRefPubMed
33.
Gascoigne KE, Taylor SS. Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs. Cancer Cell. 2008;14(2):111–22.CrossRefPubMed
34.
Huang HC, Shi J, Orth JD, Mitchison TJ. Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell. 2009;16(4):347–58.CrossRefPubMedPubMedCentral
35.
Kidokoro T, Tanikawa C, Furukawa Y, Katagiri T, Nakamura Y, Matsuda K. CDC20, a potential cancer therapeutic target, is negatively regulated by p53. Oncogene. 2008;27(11):1562–71.CrossRefPubMed
36.
Ding ZY, Wu HR, Zhang JM, Huang GR, Ji DD. Expression characteristics of CDC20 in gastric cancer and its correlation with poor prognosis. Int J Clin Exp Pathol. 2014;7(2):722–7.PubMedPubMedCentral
37.
Karra H, Repo H, Ahonen I, Löyttyniemi E, Pitkänen R, Lintunen M, et al. CDC20 and securin overexpression predict short-term breast cancer survival. Br J Cancer. 2014;110(12):2905–13.CrossRefPubMedPubMedCentral
38.
Kim Y, Choi JW, Lee JH, Kim YS. MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix. Int J Gynecol Pathol. 2014;33(5):517–23.CrossRefPubMed
39.
Li J, Gao JZ, Du JL, Huang ZX, Wei LX. Increased CDC20 expression is associated with development and progression of hepatocellular carcinoma. Int J Oncol. 2014;45(4):1547–55.PubMed
40.
Ouellet VGM, Le Page C, Filali-Mouhim A, Lussier C, Tonin PN, Provencher DM, et al. Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer. Int J Cancer. 2006;119(3):599–607.CrossRefPubMed
Metadata
Title
A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage
Authors
Mariana F. Gayyed
Nehad M. R. Abd El-Maqsoud
Ehab Rifat Tawfiek
Saad Abdelnaby A. El Gelany
Mohamed Fathy Abdel Rahman
Publication date
01-01-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 1/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3808-1

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