Hostname: page-component-848d4c4894-ttngx Total loading time: 0 Render date: 2024-04-30T11:33:07.649Z Has data issue: false hasContentIssue false
  • English
  • Français

Expression of 14-3-3 sigma, cyclin-dependent kinases 2 and 4, p16, and Epstein–Barr nuclear antigen 1 in nasopharyngeal carcinoma

Published online by Cambridge University Press:  24 January 2014

H-H Huang ,
C-H Chen ,
S-C Huang ,
C-H Yang  and
C-F Hwang
H-H Huang
Affiliation:
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
C-H Chen
Affiliation:
Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
S-C Huang
Affiliation:
Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
C-H Yang
Affiliation:
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
C-F Hwang*
Affiliation:
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
*
Address for correspondence: Dr Chung-Feng Hwang, Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung District, Kaohsiung 833, Taiwan Fax: +886 7 7313855 E-mail: cfhwang@hotmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

The protein 14-3-3 sigma plays a role in cell cycle arrest by sequestering cyclin-dependent kinase 1 cyclin B1 complexes, as well as cyclin-dependent kinases 2 and 4, hence its definition as a cyclin-dependent kinase inhibitor. However, the nature of the interaction between these biological markers in nasopharyngeal carcinoma is unknown. This study aimed to investigate whether altered expression of these markers contributes to nasopharyngeal carcinogenesis.

Methods:

The study population consisted of 30 nasopharyngeal carcinoma patients and 10 patients without nasopharyngeal carcinoma. The nasopharyngeal carcinoma cell lines TW02, TW04 and Hone-1 were also assessed. We analysed levels of messenger RNA and protein for the p16 gene and the 14-3-3 sigma, Epstein–Barr nuclear antigen 1, and cyclin-dependent kinase 2 and 4 proteins, in nasopharyngeal carcinoma tissue specimens and cell lines and in normal nasopharyngeal tissue.

Results:

Protein and messenger RNA levels for cyclin-dependent kinase 2 and Epstein–Barr nuclear antigen 1 were significantly higher in nasopharyngeal carcinoma compared with normal tissue, while levels of cyclin-dependent kinase 4 generally were not; results for 14-3-3 sigma varied. Nasopharyngeal carcinoma patients had diminished p16 gene expression, compared with normal tissue.

Conclusion:

Levels of cyclin-dependent kinase 2 and Epstein–Barr nuclear antigen 1 were significantly higher in nasopharyngeal carcinoma than in normal tissue, while p16 gene expression was diminished. These three proteins may contribute to nasopharyngeal carcinogenesis.

Keywords

Nasopharyngeal Cancer14-3-3 Sigma Protein, HumanCyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4Cyclin-Dependent Kinase Inhibitor p16
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 128 , Issue 2 , February 2014 , pp. 134 - 141
Copyright
Copyright © JLO (1984) Limited 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Baba, Y, Tsukuda, M, Mochimatsu, I, Furukawa, S, Kagata, H, Satake, K et al. Reduced expression of p16 and p27 proteins in nasopharyngeal carcinoma. Cancer Detect Prev 2001;25:414–19Google ScholarPubMed
2Al-Sarraf, M, LeBlanc, M, Giri, PG, Fu, KK, Cooper, J, Vuong, T et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998;16:1310–17CrossRefGoogle ScholarPubMed
3Prasad, GL, Valverius, EM, McDuffie, E, Cooper, HL. Complementary DNA cloning of a novel epithelial cell marker protein, HME1, that may be down-regulated in neoplastic mammary cells. Cell Growth Differ 1992;3:507–13Google ScholarPubMed
4Yaffe, MB. How do 14-3-3 proteins work? – Gatekeeper phosphorylation and the molecular anvil hypothesis. FEBS Lett 2002;513:53–7Google Scholar
5Hermeking, H, Lengauer, C, Polyak, K, He, TC, Zhang, L, Thiagalingam, S et al. 14-3-3 sigma is a p53–regulated inhibitor of G2/M progression. Mol Cell 1997;1:3–11Google Scholar
6Chan, TA, Hermeking, H, Lengauer, C, Kinzler, KW, Vogelstein, B. 14-3-3 Sigma is required to prevent mitotic catastrophe after DNA damage. Nature 1999;401:616–20Google Scholar
7Laronga, C, Yang, HY, Neal, C, Lee, MH. Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression. J Biol Chem 2000;275:23106–12CrossRefGoogle ScholarPubMed
8Iwata, N, Yamamoto, H, Sasaki, S, Itoh, F, Suzuki, H, Kikuchi, T et al. Frequent hypermethylation of CpG islands and loss of expression of the 14-3-3 sigma gene in human hepatocellular carcinoma. Oncogene 2000;19:5298–302Google Scholar
9Osada, H, Tatematsu, Y, Yatabe, Y, Nakagawa, T, Konishi, H, Harano, T et al. Frequent and histological type-specific inactivation of 14-3-3 sigma in human lung cancers. Oncogene 2002;21:2418–24Google Scholar
10Kaneuchi, M, Sasaki, M, Tanaka, Y, Shiina, H, Verma, M, Ebina, Y et al. Expression and methylation status of 14-3-3 sigma gene can characterize the different histological features of ovarian cancer. Biochem Biophys Res Commun 2004;316:1156–62Google Scholar
11Perathoner, A, Pirkebner, D, Brandacher, G, Spizzo, G, Stadlmann, S, Obrist, P et al. 14-3-3 sigma expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Clin Cancer Res 2005;11:3274–9Google Scholar
12Sato, N, Maitra, A, Fukushima, N, van Heek, NT, Matsubayashi, H, Iacobuzio-Donahue, CA et al. Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinoma. Cancer Res 2003;63:4158–66Google ScholarPubMed
13Sano, T, Shimooka, H, Weixa, P, Segawa, A, Jian, Z, Motegi, A et al. Immunohistochemical expression of 14-3-3 sigma protein in various histological subtypes of uterine cervical cancers. Pathol Int 2004;54:743–50Google Scholar
14Bhatia, K, Siraj, AK, Hussain, A, Bu, R, Gutierrez, MI. The tumor suppressor gene 14-3-3 sigma is commonly methylated in normal and malignant lymphoid cells. Cancer Epidemiol Biomarkers Prev 2003;12:165–9Google ScholarPubMed
15Hwang, CF, Huang, HY, Chen, CH, Chien, CY, Hsu, YC, Li, CF et al. Enhancer of zeste homolog 2 overexpression in nasopharyngeal carcinoma: an independent poor prognosticator that enhances cell growth. Int J Radiat Oncol Biol Phys 2012;82:597–604Google Scholar
16Tsao, SW, Liu, Y, Wang, X, Yuen, PW, Leung, SY, Yuen, ST et al. The association of E-cadherin expression and the methylation status of the E-cadherin gene in nasopharyngeal carcinoma cells. Eur J Cancer 2003;39:524–31CrossRefGoogle ScholarPubMed
17Moore, C, Shen, XD, Gao, F, Busuttil, RW, Coito, AJ. Fibronectin-alpha4beta1 integrin interactions regulate metalloproteinase-9 expression in steatotic liver ischemia and reperfusion injury. Am J Pathol 2007;170:567–77Google Scholar
18Ko, MT, Su, CY, Huang, SC, Chen, CH, Hwang, CF. Overexpression of cyclin E messenger ribonucleic acid in nasopharyngeal carcinoma correlates with poor prognosis. J Laryngol Otol 2009;123:1021–6Google Scholar
19Mustafa, T, Klonisch, T, Hombach-Klonisch, S, Kehlen, A, Schmutzler, C, Koehrle, J et al. Expression of CD97 and CD55 in human medullary thyroid carcinomas. Int J Oncol 2004;24:285–94Google Scholar
20Lin, CT, Chan, WY, Chen, W, Huang, HM, Wu, HC, Hsu, MM et al. Characterization of seven newly established nasopharyngeal carcinoma cell lines. Lab Invest 1993;68:716–27Google ScholarPubMed
21Lin, CT, Wong, CI, Chan, WY, Tzung, KW, Ho, JK, Hsu, MM et al. Establishment and characterization of two nasopharyngeal carcinoma cell lines. Lab Invest 1990;62:713–24Google Scholar
22Glaser, R, Zhang, HY, Yao, KT, Zhu, HC, Wang, FX, Li, GY et al. Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas. Proc Natl Acad Sci U S A 1989;86:9524–8Google Scholar
23Nasopharyngeal carcinoma. In: Edge, SB, Byrd, DR, Compton, CC, Fritz, AG, Greene, FL, Trotti, A, eds. AJCC Cancer Staging Manual, 7th edn.New York: Springer, 2010;291–16Google ScholarPubMed
24Huang, WG, Cheng, AL, Chen, ZC, Peng, F, Zhang, PF, Li, MY et al. Targeted proteomic analysis of 14-3-3 sigma in nasopharyngeal carcinoma. Int J Biochem Cell Biol 2010;42:137–47CrossRefGoogle Scholar
25Nakayama, H, Sano, T, Motegi, A, Oyama, T, Nakajima, T. Increasing 14-3-3 sigma expression with declining estrogen receptor alpha and estrogen-responsive finger protein expression defines malignant progression of endometrial carcinoma. Pathol Int 2005;55:707–15Google Scholar
26Umbricht, CB, Evron, E, Gabrielson, E, Ferguson, A, Marks, J, Sukumar, S. Hypermethylation of 14-3-3 sigma (stratifin) is an early event in breast cancer. Oncogene 2001;20:3348–53CrossRefGoogle ScholarPubMed
27Ferguson, AT, Evron, E, Umbricht, CB, Pandita, TK, Chan, TA, Hermeking, H et al. High frequency of hypermethylation at the 14-3-3 sigma locus leads to gene silencing in breast cancer. Proc Natl Acad Sci U S A 2000;97:6049–54CrossRefGoogle ScholarPubMed
28Moreira, JM, Ohlsson, G, Rank, FE, Celis, JE. Down-regulation of the tumor suppressor protein 14-3-3 sigma is a sporadic event in cancer of the breast. Mol Cell Proteomics 2005;4:555–69Google Scholar
29Villaret, DB, Wang, T, Dillon, D, Xu, J, Sivam, D, Cheever, MA et al. Identification of genes overexpressed in head and neck squamous cell carcinoma using a combination of complementary DNA subtraction and microarray analysis. Laryngoscope 2000;110:374–81Google Scholar
30Bhawal, UK, Sugiyama, M, Nomura, Y, Kuniyasu, H, Tsukinoki, K. Loss of 14-3-3 sigma protein expression and presence of human papillomavirus type 16 E6 in oral squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2008;134:1055–9CrossRefGoogle ScholarPubMed
31Okami, K, Reed, AL, Cairns, P, Koch, WM, Westra, WH, Wehage, S et al. Cyclin D1 amplification is independent of p16 inactivation in head and neck squamous cell carcinoma. Oncogene 1999;18:3541–5Google Scholar
32Dublin, EA, Patel, NK, Gillett, CE, Smith, P, Peters, G, Barnes, DM. Retinoblastoma and p16 proteins in mammary carcinoma: their relationship to cyclin D1 and histopathological parameters. Int J Cancer 1998;79:71–5Google Scholar
33Hwang, CF, Cho, CL, Huang, CC, Wang, JS, Shih, YL, Su, CY et al. Loss of cyclin D1 and p16 expression correlates with local recurrence in nasopharyngeal carcinoma following radiotherapy. Ann Oncol 2002;13:1246–51CrossRefGoogle ScholarPubMed
34Zhao, XR, Deng, L, Weng, XX. The effects of exogenous p16 expression on CDK4, Cyclin D1 and pRb in nasopharyngeal carcinoma cell lines [in Chinese]. Hunan Yi Ke Da Xue Xue Bao 2000;25:428–30Google ScholarPubMed
35Brooks, L, Yao, QY, Rickinson, AB, Young, LS. Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J Virol 1992;66:2689–97Google Scholar