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Cellular and Molecular Biology Letters

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Volume 13, Issue 3

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The tumor supressor function of STGC3 and its reduced expression in nasopharyngeal carcinoma

Xiu-Sheng He / Min Deng / Shuai Yang / Zhi-Qiang Xiao / Qiao Luo / Zhi-min He / Bo Hu / Zhu-Chu Chen
Published Online: 2008-07-07 | DOI: https://doi.org/10.2478/s11658-008-0006-9

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Abstract

STGC3 is a novel candidate tumor suppressor gene that was found to be associated with nasopharyngeal carcinoma (NPC) via the cDNA cloning and RACE processes. The biological function of the STGC3 protein and its expression level in nasopharyngeal carcinoma remain unknown. This study aimed to evaluate the STGC3 protein expression level in NPC and to investigate the inhibitory function of STGC3 as a candidate tumor suppressor gene. We assessed the expression of the STGC3 protein in NPC biopsies and normal control specimens via Western blot and immunohistochemical analysis. The expression of STGC3 as induced by doxycycline (Dox) via a tetracycline (Tet)-regulated system in human nasopharyngeal carcinoma cell line CNE2 was also established, and the effect of STGC3 restoration on the biological behavior of CNE2 was observed. A reduced level of STGC3 expression (0.978 ± 0.213 versus 0.324 ± 0.185, P < 0.05) was detected in NPC versus normal nasopharyngeal tissue by Western blot assay. Immunohistochemical assays for STGC3 detected positive staining in the nuclei and cytoplasm of epithelial cells, and the positive expression rate in NPC, 8 of 21 (38%), was lower than that in normal nasopharynx samples, 16 of 22 (72%). After STGC3 expression was restored, the growth capacity and clone formation potential of CNE2 cells in soft agar were significantly suppressed, and the cell percentage in G0/G1 phase increased, while the percentage of cells entering the S and G2 phases decreased. This indicates that an abnormality in STGC3 expression is associated with nasopharyngeal carcinogenesis and that it may play an important role in controlling cell growth and regulating the cell cycle.

Keywords: Nasopharyngeal neoplasm; STGC3; Gene expression; Tet-on system

  • [1] Ho, J.H.C. An epidemiologic and clinical study of nasopharyngeal carcinoma. Int. Radiat. Oncol. Biol. Phys. 4 (1978) 183–205. CrossrefGoogle Scholar

  • [2] Zheng, Y.M., Tuppin, P. and Hubert, A. The environmental and dietary risk factors for nasopharyngeal carcinoma: a case-control study in Zangwu County, Guangxi, China. Br. J. Cancer 69 (1994) 508–514. Google Scholar

  • [3] Ward, M.H., Pan, W.H., Cheng, Y.J., Li, F.H., Brinton, L.A., Chen, C.J., Hsu, M.M., Chen, I.H., Levine, P.H., Yang, C.S. and Hildesheim, A. Dietary exposure to nitrite and nitrosamines and risk of nasopharyngeal carcinoma in Taiwan. Int. J. Cancer 86 (2000) 603–609. http://dx.doi.org/10.1002/(SICI)1097-0215(20000601)86:5<603::AID-IJC1>3.0.CO;2-HCrossrefGoogle Scholar

  • [4] Krishna, S.M., James, S., Kattoor, J. and Balaram, P. Serum EBV DNA as a biomarker in primary nasopharyngeal carcinoma of Indian origin. Jpn. J._Clin. Oncol. 34 (2004) 307–311. http://dx.doi.org/10.1093/jjco/hyh055CrossrefGoogle Scholar

  • [5] Yang, X.R., Diehl, S., Pfeiffer, R., Chen, C.J., Hsu, W.L., Dosemeci, M., Cheng, Y.J., Sun, B., Goldstein, A.M. and Hildesheim, A. Chinese and American Genetic Epidemiology of NPC Study Team. Evaluation of risk factors for nasopharyngeal carcinoma in high-risk nasopharyngeal carcinoma families in Taiwan. Cancer Epidemiol. Biomarkers Prev. 14 (2005) 900–905. http://dx.doi.org/10.1158/1055-9965.EPI-04-0680CrossrefGoogle Scholar

  • [6] Thornburg, N.J., Pathmanathan, R. and Raab-Traub, N. Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma. Cancer Res. 63 (2003) 8293–8301. Google Scholar

  • [7] Horikawa, T., Sheen, T.S., Takeshita, H., Sato, H., Furukawa, M. and Yoshizaki, T. Induction of c-Met proto-oncogene by Epstein-Barr virus latent membrane protein-1 and the correlation with cervical lymph node metastasis of nasopharyngeal carcinoma. Am. J. Pathol. 159 (2001) 27–33. Google Scholar

  • [8] Sarac, S., Akyol, M.U., Kanbur, B., Poyraz, A., Akyol, G., Yilmaz, T. and Sungur, A. Bcl-2 and LMP1 expression in nasopharyngeal carcinomas. Am. J. Otolaryngol. 22 (2001) 377–382. http://dx.doi.org/10.1053/ajot.2001.28071Google Scholar

  • [9] Qian, C.N., Guo, X., Cao, B., Kort, E.J., Lee, C.C., Chen, J., Wang, L.M., Mai, W.Y., Min, H.Q., Hong, M.H., Vande, Woude, G.F., Resau, J.H. and The, B.T. Met protein expression level correlates with survival in patients with late-stage nasopharyngea carcinoma. Cancer Res. 62 (2002) 589–596. Google Scholar

  • [10] Lo, K.W., Cheung, S.T., Leung, S.F., van Hasselt, A., Tsang, Y.S., Mak, K.F., Chung, Y.F., Woo, J.K., Lee, J.C. and Huang, D.P. Hypermethylation of the p16 gene in nasopharyngeal carcinoma. Cancer Res. 56 (1996) 2721–2725. Google Scholar

  • [11] Yan, J., Fang, Y., Huang, B.J., Liang, Q.W., Wu, Q.L. and Zeng, Y.X. Absence of evidence for HER2 amplication in nasopharyngeal carcinoma. Cancer Genet. Cytogenet. 132 (2002) 116–119. http://dx.doi.org/10.1016/S0165-4608(01)00542-8CrossrefGoogle Scholar

  • [12] Sheu, L.F., Chen, A., Tseng, H.H., Leu, F.J., Lin, J.K., Ho, K.C. and Meng, C.L. Assessment of p53 expression in nasopharyngeal carcinoma. Hum. Pathol. 26 (1995) 380–386. http://dx.doi.org/10.1016/0046-8177(95)90137-XGoogle Scholar

  • [13] Hui, A.B., Lo, K.W., Kwong, J., Lam, E.C., Chan, S.Y., Chow, L.S., Chan, A.S., Teo, P.M. and Huang, D.P. Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma. Mol. Carcinog. 38 (2003) 170–178. http://dx.doi.org/10.1002/mc.10156CrossrefGoogle Scholar

  • [14] Shao, J.Y., Wang, H.Y., Huang, X.M., Feng, Q.S., Huang, P., Feng, B.J., Huang, L.X., Yu, X.J., Li, J.T., Hu, L.F., Ernberg, I. and Yi, X.Z. Genomewide allelotype analysis of sporadic primary nasopharyngeal carcinoma from southern China. Int. J. Oncol. 17 (2000) 1267–1275. Google Scholar

  • [15] Deng, L., Jing, N., Tan, G., Zhou, M., Zhan, F., Xie, Y., Cao, L. and Li, G. A common region of allelic loss on chromosome region3p25.3-26.3 in nasopharyngeal carcinoma. Genes Chromosomes Cancer 23 (1998) 21–22. http://dx.doi.org/10.1002/(SICI)1098-2264(199809)23:1<21::AID-GCC4>3.0.CO;2-8CrossrefGoogle Scholar

  • [16] Shao, J., Li, Y., Wu, Q., Liang, X., Yu, X., Huang, L., Hou, J., Huang, X., Ernberg, I., Hu, L.F. and Zeng, Y. High frequency loss of heterozygosity on the long arms of chromosomes 13 and 14 in nasopharyngeal carcinoma in Southern China. Chin. Med. J. 115 (2002) 571–575. Google Scholar

  • [17] Xiong, W., Zeng, Z.Y., Xia, J.H., Xia, K., Shen, S.R., Li, X.L., Hu, D.X., Tan, C., Xiang, J.J., Zhou, J., Deng, H., Fan, S.Q., Li, W.F., Wang J.R., Zhou, M., Zhu, S.G., Lu, H.B., Qian, J., Zhang, B.C., Wang, J.R., Ma, J., Xiao, B.Y., Huang, H., Zhang, Q.H., Zhou, Y.H., Luo, X.M., Zhou, H.D., Yang, Y.X., Dai, H.P., Feng, G.Y., Pan, Q., Wu, L.Q., He, L. and Li, G.Y. A susceptibility locus at chromosome 3p21 linked to familial nasopharyngeal carcinoma. Cancer Res. 64 (2004) 1972–1974. http://dx.doi.org/10.1158/0008-5472.CAN-03-3253CrossrefGoogle Scholar

  • [18] He, X.S., Chen, Z.C., Tian, F., Xiao, Z.Q., He, Z.M., Guan, Y.J., Li, F., He, C.M. and Yuan, J.H. Identification of down-regulated expressed sequence tag at chromosome 3p21 in nasopharyngeal carcinoma. Ai Zheng. 22 (2003) 1–5. Google Scholar

  • [19] He, X.S., Xiao, Z.Q., Chen, Z.C., Zhao, S.P., Zhu, J.H., He, Z.M., Li, Y.J., Tian, F. and Yu, Y.H. Molecular cloning and functional analysis of STGC3-a novel gene on chromosome 3p21. Ai Zheng. 23 (2004) 1110–1115. Google Scholar

  • [20] Andac, Z., Sasaki, T., Mann, K., Bracaccio, A., Deutzman, R. and Timpl, R. Analysis of heparin, alpha-dystroglycan and sulfatide binding to the G domain of the laminin alpha1 chain by site-directed mutagenesis. J. Mol. Biol. 287 (1999) 253–264. http://dx.doi.org/10.1006/jmbi.1999.2606CrossrefGoogle Scholar

  • [21] Talts, J.F., Andac, Z., Gohring, W., Brancaccio, A. and Timpl, R. Binding of the G domains of laminin alpha1 and alpha2 chains and perlecan to heparin, sulfatides, alpha-dystroglycan and several extracellular matrix proteins. EMBO. J. 18 (1999) 863–870. http://dx.doi.org/10.1093/emboj/18.4.863CrossrefGoogle Scholar

  • [22] Talts, J.F. and Timpl, R. Mutation of a basic sequence in the laminin alpha2LG3 module leads to a lack of proteolytic processing and has different effects on beta1 integrin-mediated cell adhesion and alphadystroglycan binding. FEBS. Lett. 458 (1999) 319–323. http://dx.doi.org/10.1016/S0014-5793(99)01180-1Google Scholar

  • [23] Yurchenco, P.D., Sung, U., Ward, M.D., Yamada, Y. and O’Rear, J.J. Recombinant laminin G domain mediates myoblast adhesion and heparin binding. J. Biol. Chem. 268 (1993) 8356–8365. Google Scholar

  • [24] Sung, U., O’Rear, J.J. and Yurchenco, P.D. Localization of heparin binding activity in recombinant laminin G domain. Eur. J. Biochem. 250 (1997) 138–143. http://dx.doi.org/10.1111/j.1432-1033.1997.00138.xCrossrefGoogle Scholar

  • [25] Sambrook, J., Fritsch, E.F. and Maniatis, T. Molecular Cloning. A Laboratory Manual, Ed. I. Cold Spring Harbor Laboratory Press, New York, 1989. Google Scholar

  • [26] Gossen, M. and Bujard, H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc. Natl. Acad. Sci. 89 (1992) 5547–5551. http://dx.doi.org/10.1073/pnas.89.12.5547CrossrefGoogle Scholar

  • [27] Gossen, M., Freundlieb, S., Bender, G., Muller, G., Hillen, W. and Bujard, H. Transcriptional activation by tetracyclines in mammalian cells. Science 268 (1995) 1766–17699. http://dx.doi.org/10.1126/science.7792603CrossrefGoogle Scholar

  • [28] Kashima, Y., Minami, K. and Seino, S. Establishment of a Tet-on gene expression system in glucose-responsive and-unresponsive MIN6 cells. Diabetes 50 (2001) S133. http://dx.doi.org/10.2337/diabetes.50.2007.S133CrossrefGoogle Scholar

  • [29] Wang, D., Grammer, J.R., Cobbs, C.S., Stewart, J.E. Jr., Liu Z., Rhoden, R., Hecker, T.P., Ding, Q. and Gladson, C.L. P125 focal adhesion kinase promotes malignant astrocytoma cell proliferation in vivo. J. Cell Sci. 113 (2000) 4221–4230. Google Scholar

  • [30] Kobayashi, T., Sawa, H., Morikawa, J., Zhang, W. and Shiku, H. Bax induction activates apoptotic cascade via mitochondrial cytochrome crelease and Bax overexpression enhances apoptosis induced by chemotherapeutic agents in DLD-1 colon cancer cells. JPN. J. Cancer Res. 91 (2000) 1264–1268. Google Scholar

About the article

Published Online: 2008-07-07

Published in Print: 2008-09-01

Citation Information: Cellular and Molecular Biology Letters, Volume 13, Issue 3, Pages 339–352, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-008-0006-9.

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© 2008 University of Wrocław, Poland. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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