CDK3 expression and its clinical significance in human nasopharyngeal carcinoma

Wang,Liang; Hu,Hong‑Yi; Lin,Yi‑Ling; Zhao,Zhi‑Xiang; Tan,Lu; Yu,Peng; Wan,Hui‑Juan; Jin,Zhe; Zheng,Duo

doi:10.3892/mmr.2014.2095

CDK3 expression and its clinical significance in human nasopharyngeal carcinoma

Authors:
- Liang Wang
- Hong‑Yi Hu
- Yi‑Ling Lin
- Zhi‑Xiang Zhao
- Lu Tan
- Peng Yu
- Hui‑Juan Wan
- Zhe Jin
- Duo Zheng
View Affiliations

Affiliations: Department of Basic Medicine, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China, Department of Otolaryngology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
Published online on: March 31, 2014 https://doi.org/10.3892/mmr.2014.2095
Pages: 2582-2586

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the current study was to investigate the expression of cyclin‑dependent kinase 3 (CDK3) in human nasopharyngeal carcinoma (NPC) and to evaluate its association with the clinicopathological characteristics of patients with NPC. CDK3 expression was examined in three NPC cell lines and one nasopharyngeal epithelial cell line by western blot analysis and in 94 specimens of NPC and 40 specimens of inflamed nasopharyngeal tissue by immunohistochemistry staining. CDK3 was overexpressed in the three NPC cell lines, 5‑8F, CNE1 and CNE2, compared with the NP‑69 nasopharyngeal epithelial cell line, and was primarily expressed in the cytoplasm. The frequency of CDK3 expression was significantly higher in NPC specimens (67%) compared with inflamed nasopharyngeal tissue specimens (12.5%; P<0.001). CDK3 expression was associated with the degree of infiltration, lymph node metastasis and tumor node metastasis clinical staging, respectively, (P<0.001) in patients with NPC. These results revealed that the expression of CDK3 is associated with the progression of NPC, and may be a potential biomarker for prediction of the prognosis of patients with NPC.

View Figures

View References

1	Mutirangura A, Tanunyutthawongese C, Pornthanakasem W, et al: Genomic alterations in nasopharyngeal carcinoma: loss of heterozygosity and Epstein-Barr virus infection. Br J Cancer. 76:770–776. 1997. View Article : Google Scholar : PubMed/NCBI
2	Wee JT, Ha TC, Loong SL and Qian CN: Is nasopharyngeal cancer really a ‘Cantonese cancer’? Chin J Cancer. 29:517–526. 2010.
3	No authors listed. Cancer incidence in five continents. VII. IARC Sci Publ; pp. i–xxxiv. pp. 1–1240. 1997
4	Chow E, Payne D, O’Sullivan B, et al: Radiotherapy alone in patients with advanced nasopharyngeal cancer: comparison with an intergroup study. Is combined modality treatment really necessary? Radiother Oncol. 63:269–274. 2002. View Article : Google Scholar
5	al-Sarraf M and McLaughlin PW: Nasopharynx carcinoma: choice of treatment. Int J Radiat Oncol Biol Phys. 33:761–763. 1995. View Article : Google Scholar : PubMed/NCBI
6	Chua DT, Sham JS and Au GK: A phase II study of capecitabine in patients with recurrent and metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Oral Oncol. 39:361–366. 2003. View Article : Google Scholar
7	Meyerson M, Enders GH, Wu CL, et al: A family of human cdc2-related protein kinases. EMBO J. 11:2909–2917. 1992.PubMed/NCBI
8	Miyata Y, Liu Y, Jankovic V, et al: Cyclin C regulates human hematopoietic stem/progenitor cell quiescence. Stem Cells. 28:308–317. 2010.PubMed/NCBI
9	Rao HV, Thirumangalakudi L and Grammas P: Cyclin C and cyclin dependent kinases 1, 2 and 3 in thrombin-induced neuronal cell cycle progression and apoptosis. Neurosci Lett. 450:347–350. 2009. View Article : Google Scholar : PubMed/NCBI
10	Sage J, Miller AL, Pérez-Mancera PA, Wysocki JM and Jacks T: Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry. Nature. 424:223–228. 2003. View Article : Google Scholar : PubMed/NCBI
11	Hofmann F and Livingston DM: Differential effects of cdk2 and cdk3 on the control of pRb and E2F function during G1 exit. Genes Dev. 10:851–861. 1996. View Article : Google Scholar : PubMed/NCBI
12	Ren S and Rollins BJ: Cyclin C/cdk3 promotes Rb-dependent G0 exit. Cell. 117:239–251. 2004. View Article : Google Scholar : PubMed/NCBI
13	van den Heuvel S and Harlow E: Distinct roles for cyclin-dependent kinases in cell cycle control. Science. 262:2050–2054. 1993.PubMed/NCBI
14	Lee JY, Jeong W, Kim JH, et al: Distinct expression pattern and post-transcriptional regulation of cell cycle genes in the glandular epithelia of avian ovarian carcinomas. PLoS One. 7:e515922012. View Article : Google Scholar
15	Zheng D, Cho YY, Lau AT, et al: Cyclin-dependent kinase 3-mediated activating transcription factor 1 phosphorylation enhances cell transformation. Cancer Res. 68:7650–7660. 2008. View Article : Google Scholar
16	Cho YY, Tang F, Yao K, et al: Cyclin-dependent kinase-3-mediated c-Jun phosphorylation at Ser63 and Ser73 enhances cell transformation. Cancer Res. 69:272–281. 2009. View Article : Google Scholar : PubMed/NCBI
17	Bullrich F, MacLachlan TK, Sang N, et al: Chromosomal mapping of members of the cdc2 family of protein kinases, cdk3, cdk6, PISSLRE, and PITALRE, and a cdk inhibitor, p27Kip1, to regions involved in human cancer. Cancer Res. 55:1199–1205. 1995.PubMed/NCBI
18	Mao YP, Li WF, Chen L, et al: A clinical verification of the Chinese 2008 staging system for nasopharyngeal carcinoma. Ai Zheng. 28:1022–1028. 2009.(In Chinese).
19	Malumbres M and Barbacid M: Mammalian cyclin-dependent kinases. Trends Biochem Sci. 30:630–641. 2005. View Article : Google Scholar
20	Schang LM, Bantly A and Schaffer PA: Explant-induced reactivation of herpes simplex virus occurs in neurons expressing nuclear cdk2 and cdk4. J Virol. 76:7724–7735. 2002. View Article : Google Scholar : PubMed/NCBI
21	Keezer SM and Gilbert DM: Evidence for a pre-restriction point Cdk3 activity. J Cell Biochem. 85:545–552. 2002. View Article : Google Scholar : PubMed/NCBI
22	Braun K, Hölzl G, Soucek T, Geisen C, Möröy T and Hengstschläger M: Investigation of the cell cycle regulation of cdk3-associated kinase activity and the role of cdk3 in proliferation and transformation. Oncogene. 17:2259–2269. 1998. View Article : Google Scholar : PubMed/NCBI
23	Alessandrini A, Chiaur DS and Pagano M: Regulation of the cyclin-dependent kinase inhibitor p27 by degradation and phosphorylation. Leukemia. 11:342–345. 1997. View Article : Google Scholar : PubMed/NCBI
24	Baba Y, Tsukuda M, Mochimatsu I, et al: Reduced expression of p16 and p27 proteins in nasopharyngeal carcinoma. Cancer Detect Prev. 25:414–419. 2001.PubMed/NCBI
25	Pan Y, Zhang Q, Tian L, et al: Jab1/CSN5 negatively regulates p27 and plays a role in the pathogenesis of nasopharyngeal carcinoma. Cancer Res. 72:1890–1900. 2012. View Article : Google Scholar : PubMed/NCBI
26	Shih LC, Tsai CW, Tsai MH, et al: Association of cyclin D1 genotypes with nasopharyngeal carcinoma risk. Anticancer Res. 32:1093–1098. 2012.PubMed/NCBI
27	Acikalin MF, Etiz D, Gurbuz MK, Ozudogru E, Canaz F and Colak E: Prognostic significance of galectin-3 and cyclin D1 expression in undifferentiated nasopharyngeal carcinoma. Med Oncol. 29:742–749. 2012. View Article : Google Scholar
28	Hung MC and Link W: Protein localization in disease and therapy. J Cell Sci. 124:3381–3392. 2011. View Article : Google Scholar : PubMed/NCBI
29	Shapiro GI: Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 24:1770–1783. 2006. View Article : Google Scholar : PubMed/NCBI
30	Yang ES and Burnstein KL: Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm. J Biol Chem. 278:46862–46868. 2003. View Article : Google Scholar : PubMed/NCBI
31	Flores O, Wang Z, Knudsen KE and Burnstein KL: Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin-dependent kinase 2 localization and cyclin E in vitamin D-mediated growth inhibition. Endocrinology. 151:896–908. 2010. View Article : Google Scholar
32	Bryja V, Pacherník J, Vondrácek J, et al: Lineage specific composition of cyclin D-CDK4/CDK6-p27 complexes reveals distinct functions of CDK4, CDK6 and individual D-type cyclins in differentiating cells of embryonic origin. Cell Prolif. 41:875–893. 2008. View Article : Google Scholar