Expression of cyclooxygenase-2, peroxiredoxin I, peroxiredoxin 6 and nuclear factor-κB in oral squamous cell carcinoma

Lee,Eun‑Young; Kang,Ji‑Yeon; Kim,Kyoung-Won

doi:10.3892/ol.2015.3705

Expression of cyclooxygenase-2, peroxiredoxin I, peroxiredoxin 6 and nuclear factor-κB in oral squamous cell carcinoma

Authors:
- Eun‑Young Lee
- Ji‑Yeon Kang
- Kyoung-Won Kim
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Affiliations: Department of Oral and Maxillofacial Surgery, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Chungbuk 361‑711, Republic of Korea, Department of Oral and Maxillofacial Surgery, Dongtan Sacred Heart Hospital, Hallym University, Hwaseong, Gyeonggi 445‑170, Republic of Korea
Published online on: September 16, 2015 https://doi.org/10.3892/ol.2015.3705
Pages: 3129-3136

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Abstract

Tumor development and progression are multistep processes that involve local tumor growth and invasion, followed by metastasis. The aggressiveness of the tumor is the major determinant of the mortality of oral cancer patients. The present study investigates whether the expression levels of cyclooxygenase‑2 (COX‑2), nuclear factor‑κB (NF‑κB), peroxiredoxin 1 (PRDX1) and PRDX6 are associated with the development, proliferation, differentiation and recurrence of oral squamous cell carcinoma (OSCC). The mRNA expression levels of COX‑2, NF‑κB, PRDX1 and PRDX6 were examined in 50 OSCC specimens and 19 normal oral mucosae by quantitative polymerase chain reaction (qPCR). qPCR analysis showed that the mRNA levels of COX‑2 in OSCC were significantly higher than those in the normal oral mucosae (P=0.021). The expression levels of PRDX1 in high‑stage tumors (T3 and T4) were significantly elevated compared with those in low‑stage tumors (T1) (P=0.047). Additionally, the expression levels of NF‑κB in the high‑grade tumor were significantly elevated compared with those in the low‑grade tumors (P=0.030). Overall, it was indicated that the expression of COX‑2 is strongly associated with the development of OSCC. Moreover, the enhanced expression of PRDX1 and NF‑κB may function in the progression of OSCC, which serves as a useful marker for prognosis in patients with oral cancer.

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1	Bianchi B, Ferri A, Ferrari S, et al: Reconstruction of lateral through and through oro-mandibular defects following oncological resections. Microsurgery. 30:517–525. 2010. View Article : Google Scholar : PubMed/NCBI
2	Thankappan K, Kuriakose MA, Chatni SS, Sharan R, Trivedi NP, Vijayaraghavan S, Sharma M and Iyer S: Lateral arm free flap for oral tongue reconstruction: An analysis of surgical details, morbidity, and functional and aesthetic outcome. Ann Plast Surg. 66:261–266. 2011. View Article : Google Scholar : PubMed/NCBI
3	Zeno HA, Sternberger SS, Tuminelli FJ, Billotte M and Kurtz KS: Combination lower lip prosthesis retained by an intraoral component. J Prosthodont. 22:397–401. 2013. View Article : Google Scholar : PubMed/NCBI
4	Kawase-Koga Y, Mori Y, Saijo H, Hoshi K and Takato T: Reconstruction of a complex midface defect from excision of a squamous cell carcinoma, according to regional aesthetic units. Oral Surg Oral Med Oral Pathol Oral Radiol. 117:e97–e101. 2014. View Article : Google Scholar : PubMed/NCBI
5	Chiesa F, Mauri S, Tradati N, Calabrese L, Giugliano G, Ansarin M, Andrle J, Zurrida S, Orecchia R and Scully C: Surfing prognostic factors in head and neck cancer at the millennium. Oral Oncol. 35:590–596. 1999. View Article : Google Scholar : PubMed/NCBI
6	Brinkman BM and Wong DT: Disease mechanism and biomarkers of oral squamous cell carcinoma. Curr Opin Oncol. 18:228–233. 2006. View Article : Google Scholar : PubMed/NCBI
7	Babu GS, Supriya AN, Kumar Raj NG and Swetha P: Tumor markers: An overview. J Orofac Sci. 3:87–95. 2012.
8	Sudbø J and Reith A: The evolution of predictive oncology and molecular-based therapy for oral cancer prevention. Int J Cancer. 115:339–345. 2005. View Article : Google Scholar : PubMed/NCBI
9	Kujubu DA, Reddy ST, Fletcher BS and Herschman HR: Expression of the protein product of the prostaglandin synthase-2/TIS10 gene in mitogen-stimulated Swiss 3T3 cells. J Biol Chem. 268:5425–5430. 1993.PubMed/NCBI
10	Vane J: Towards a better aspirin. Nature. 367:215–216. 1994. View Article : Google Scholar : PubMed/NCBI
11	Shibata M, Kodani I, Osaki M, Araki K, Adachi H, Ryoke K and Ito H: Cyclo-oxygenase-1 and-2 expression in human oral mucosa, dysplasias and squamous cell carcinomas and their pathological significance. Oral Oncol. 41:304–312. 2005. View Article : Google Scholar : PubMed/NCBI
12	Wood ZA, Schröder E, Robin Harris J and Poole LB: Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci. 28:32–40. 2003. View Article : Google Scholar : PubMed/NCBI
13	Yanagawa T, Ishikawa T, Ishii T, Tabuchi K, Iwasa S, Bannai S, Omura K, Suzuki H and Yoshida H: Peroxiredoxin I expression in human thyroid tumors. Cancer Lett. 145:127–132. 1999. View Article : Google Scholar : PubMed/NCBI
14	Kinnula VL, Lehtonen S, Sormunen R, Kaarteenahob WR, Kang SW, Rhee SG and Soini Y: Overexpression of peroxiredoxins III, IIIV and VI in malignant mesothelioma. J Pathol. 196:316–323. 2002. View Article : Google Scholar : PubMed/NCBI
15	Chang JW, Jeon HB, Lee JH, Yoo JS, Chun JS, Kim JH and Yoo YJ: Augmented expression of peroxiredoxin I in lung cancer. Biochem Biophys Res Commun. 289:507–512. 2001. View Article : Google Scholar : PubMed/NCBI
16	Noh DY, Ahn SJ, Lee RA, Kim SW, Park IA and Chae HZ: Overexpression of peroxiredoxin in human breast cancer. Anticancer Res. 21:2085–2090. 2001.PubMed/NCBI
17	Prosperi MT, Ferbus D, Karczinski I and Goubin G: A human cDNA corresponding to a gene overexpressed during cell proliferation encodes a product sharing homology with amoebic and bacterial proteins. J Biol Chem. 268:11050–11056. 1993.PubMed/NCBI
18	Kang SW, Chae HZ, Seo MS, Kim K, Baines IC and Rhee SG: Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha. J Biol Chem. 273:6297–6302. 1998. View Article : Google Scholar : PubMed/NCBI
19	Klaunig JE, Xu Y, Isenberg JS, Bachowski S, Kolaja KL, Jiang J, Stevenson DE and Walborg EF Jr: The role of oxidative stress in chemical carcinogenesis. Environ Health Perspect. 106:289–295. 1998. View Article : Google Scholar : PubMed/NCBI
20	Fujii J and Ikeda Y: Advances in our understanding of peroxiredoxin, a multifunctional, mammalian redox protein. Redox Rep. 7:123–130. 2002. View Article : Google Scholar : PubMed/NCBI
21	Ishii T, Yamada M, Sato H, Matsue M, Taketani S, Nakayama K, Sugita Y and Bannai S: Cloning and characterization of a 23-kDa stress-induced mouse peritoneal macrophage protein. J Biol Chem. 268:18633–18636. 1993.PubMed/NCBI
22	Liu M, Lawson G, Delos M, Jamart J, Ide C, Coche E, Weynand B, Desuter G, Hamoir M, Remacle M and Marbaix E: Predictive value of the fraction of cancer cells immunolabeled for proliferating cell nuclear antigen or Ki67 in biopsies of head and neck carcinomas to identify lymph node metastasis: Comparison with clinical and radiologic examinations. Head Neck. 25:280–288. 2003. View Article : Google Scholar : PubMed/NCBI
23	Matsumoto A, Okado A, Fujii T, Fujii J, Egashira M, Niikawa N and Taniguchi N: Cloning of the peroxiredoxin gene family in rats and characterization of the fourth member. FEBS Lett. 443:246–250. 1999. View Article : Google Scholar : PubMed/NCBI
24	Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH and Van Etten RA: Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature. 424:561–565. 2003. View Article : Google Scholar : PubMed/NCBI
25	Greene FL, Page D, Morrow M, et al: Lip and oral cavity. AJCC Cancer Staging Manual (6th). (New York). Springer. 23–32. 2002.
26	Wolff H, Saukkonen K, Anttila S, Karjalainen A, Vainio H and Ristimäki A: Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res. 58:4997–5001. 1998.PubMed/NCBI
27	Shamma A, Yamamoto H, Doki Y, Okami J, Kondo M, Fujiwara Y, Yano M, Inoue M, Matsuura N, Shiozaki H and Monden M: Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus. Clin Cancer Res. 6:1229–1238. 2000.PubMed/NCBI
28	Peng JP, Su CY, Chang HC, Chai CY and Hung WC: Overexpression of cyclo-oxygenase 2 in squamous cell carcinoma of the hypopharynx. Hum Pathol. 33:100–104. 2002. View Article : Google Scholar : PubMed/NCBI
29	Banerjee AG, Gopalakrishnan VK, Bhattacharya I and Vishwanatha JK: Deregulated cyclooxygenase-2 expression in oral premalignant tissues. Mol Cancer Ther. 1:1265–1271. 2002.PubMed/NCBI
30	Yu HP, Xu SQ, Liu L, Shi LY, Cai XK, Lu WH, Lu B, Su YH and Li YY: Cyclo-oxygenase-2 expression in squamous dysplasia and squamous cell carcinoma of the esophagus. Cancer lett. 198:193–201. 2003. View Article : Google Scholar : PubMed/NCBI
31	Tsujii M and DuBois RN: Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell. 83:493–501. 1995. View Article : Google Scholar : PubMed/NCBI
32	Zhi H, Wang L, Zhang J, Zhou C, Ding F, Luo A, Wu M, Zhan Q and Liu Z: Significance of COX-2 expression in human esophageal squamous cell carcinoma. Carcinogenesis. 27:1214–1221. 2006. View Article : Google Scholar : PubMed/NCBI
33	Kase S, Osaki M, Honjo S, Adachi H, Tsujitani S, Kaibara N and Ito H: Expression of cyclo-oxygenase-2 is correlated with high intratumoral microvessel density and low apoptotic index in human esophageal squamous cell carcinomas. Virchows Arch. 442:129–135. 2003.PubMed/NCBI
34	Quan C, Cha EJ, Lee HL, Han KH, Lee KM and Kim WJ: Enhanced expression of peroxiredoxin I and 6 correlates with development, recurrence and progression of human bladder cancer. J Urol. 175:1512–1516. 2006. View Article : Google Scholar : PubMed/NCBI
35	Lehtonen ST, Svensk AM, Soini Y, Pääkkö P, Hirvikoski P, Kang SW, Säily M and Kinnula VL: Peroxiredoxins, a novel protein family in lung cancer. Int J Cancer. 111:514–521. 2004. View Article : Google Scholar : PubMed/NCBI
36	Yanagawa T, Iwasa S, Ishii T, Tabuchi K, Yusa H, Onizawa K, Omura K, Harada H, Suzuki H and Yoshida H: Peroxiredoxin I expression in oral cancer: A potential new tumor marker. Cancer Lett. 156:27–35. 2000. View Article : Google Scholar : PubMed/NCBI
37	Wen ST and Van Etten RA: The pag gene product, a stress-induced protein with antioxidant properties, is an abl SH3-binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity. Genes Dev. 11:2456–2467. 1997. View Article : Google Scholar : PubMed/NCBI
38	Prospéri MT, Ferbus D, Rouillard D and Goubin G: The pag gene product, a physiological inhibitor of c-abl tyrosine kinase, is overexpressed in cells entering S phase and by contact with agents inducing oxidative stress. FEBS Lett. 423:39–44. 1998. View Article : Google Scholar : PubMed/NCBI
39	Yanagawa T, Omura K, Harada H, Ishii T, Uwayama J, Nakaso K, Iwasa S, Koyama Y, Onizawa K, Yusa H and Yoshida H: Peroxiredoxin I expression in tongue squamous cell carcinomas as involved in tumor recurrence. Int J Oral Maxillofac Surg. 34:915–920. 2005. View Article : Google Scholar : PubMed/NCBI
40	Richmond A: NF-kappa B chemokine gene transcription and tumour growth. Nat Rev Immunol. 2:664–674. 2002. View Article : Google Scholar : PubMed/NCBI
41	Loercher A, Lee TL, Ricker JL, Howard A, Geoghegen J, Chen Z, Sunwoo JB, Sitcheran R, Chuang EY, Mitchell JB, et al: Nuclear factor-kappaB is an important modulator of the altered gene expression profile and malignant phenotype in squamous cell carcinoma. Cancer Res. 64:6511–6523. 2004. View Article : Google Scholar : PubMed/NCBI
42	Takada Y, Singh S and Aggarwal BB: Identification of a p65 peptide that selectively inhibits NF-kappa B activation induced by various inflammatory stimuli and its role in down-regulation of NF-kappaB-mediated gene expression and up-regulation of apoptosis. J Biol Chem. 279:15096–15104. 2004. View Article : Google Scholar : PubMed/NCBI
43	Wolf JS, Chen Z, Dong G, Sunwoo JB, Bancroft CC, Capo DE, Yeh NT, Mukaida N and Van Waes C: IL (interleukin)-1alpha promotes nuclear factor-kappaB and AP-1-induced IL-8 expression, cell survival and proliferation in head and neck squamous cell carcinomas. Clin Cancer Res. 7:1812–1820. 2001.PubMed/NCBI
44	Bancroft CC, Chen Z, Yeh J, Sunwoo JB, Yeh NT, Jackson S, Jackson C and Van Waes C: Effects of pharmacologic antagonists of epidermal growth factor receptor, PI3K and MEK signal kinases on NF-kappaB and AP-1 activation and IL-8 and VEGF expression in human head and neck squamous cell carcinoma lines. Int J Cancer. 99:538–548. 2002. View Article : Google Scholar : PubMed/NCBI
45	Nakayama H, Ikebe T, Beppu M and Shirasuna K: High expression levels of nuclear factor kappaB IkappaB kinase alpha and Akt kinase in squamous cell carcinoma of the oral cavity. Cancer. 92:3037–3044. 2001. View Article : Google Scholar : PubMed/NCBI