Abstract
The expression of metallothionein (MT), an intracellular ubiquitous low molecular weight protein thiol with antioxidant properties, was studied in nasopharyngeal cancer (NPC) and correlated with the apoptotic index. Immunohistochemical staining of randomly selected, formalin-fixed and paraffin-embedded normal and malignant nasopharyngeal tissues were analysed for the expression of MT using the commercially available E9 antibody directed against MT I and MT II isoforms. The corresponding apoptosis labelling indices were evaluated by the TUNEL method. Localization of MT at the ultrastructural level was studied by immunogold labelling. All the tumour sections (17 specimens) showed MT-immunopositivity. A direct correlation between the percentage of MT-positive cells and the staining intensity was noted (P< 0.001; Pearson's r = 0.95). There was absence of cytoplasmic staining and only nuclear staining (with localization in the nucleoplasm) was demonstrated in the tumour cells. In normal epithelium of the nasopharynx, the basal layer was stained. An inverse relationship was observed between the level of MT expression and the apoptotic index in the NPC tissues (P = 0.0059; Pearson's r = –0.6380). The results suggest that overexpression of MT in NPC may protect the tumour cells from entering into the apoptotic process and thereby contribute to tumour expansion. Preferential localization of MT in the nuclei of NPC cells may possibly enhance radioresistance since radiotherapy is known to eradicate tumour cells by free radical-induced apoptosis. © 2000 Cancer Research Campaign
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References
Aoki Y and Suzuki KT (1991) Detection of metallothionein by Western blotting. Methods Enzymol 205: 108–114
Bahnson RR, Banner BF, Ernstoff MS, Lazo JS and Cherian MG (1991) Immunohistochemical localisation of metallothionien in transitional cell carcinoma of the bladder. J Urol 146: 1518–1520
Bailet JW, Mark RF, Abemayor E, Lee SP, Tran LM, Julliard G and Ward PH (1992) Nasopharyngeal carcinoma: treatment results with primary radiation therapy. Laryngoscope 102: 965–972
Bay BH, Chan YG, Fong CM and Leong HK (1997) Differential cellular zinc levels in metastatic and primary nasopharyngeal carcinoma. Int J Oncol 11: 745–748
Bay BH, Chan YG, Tuck YK and Leong HK (1998) Electron microscopic observations and X-ray microanalysis of a multinucleated giant cell. J Electron Microsc 47: 359–361
Briehl MM and Baker AF (1996) Modulation of the antioxidant defence as a factor in apoptosis. Cell Death Differ 3: 63–70
Buttke TM and Sandstrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15: 7–10
Cai L, Wang GJ, Xu ZL, Deng DX, Chakrabarti S and Cherian MG (1998) Metallothionein and apoptosis in primary human hepatocellular carcinoma from Northern China. Anticancer Res 18: 4667–4672
Cherian MG, Howell SB, Imura N, Klaassen CD, Koropatnick J, Lazo JS and Waalkes MP (1994) Role of metallothionein in carcinogenesis. Toxicol Applied Pharmacol 126: 1–5
Germain I, Tetu B, Brisson J, Mondor M and Cherian MG (1996) Markers of chemoresistance in ovarian carcinomas: an immunohistochemical study of 86 cases. Int J Gynecol Pathol 15: 54–62
Jin R, Bay BH, Tan PH and Tan BKH (1999) Metallothionein expression and zinc levels in invasive ductal carcinoma of the breast. Oncol Rep 6: 871–875
Kagi JHR and Schaffer A (1988) Biochemistry of metallothionein. Biochemistry 27: 8509–8514
Kelley SL, Basu A, Teicher BA, Hacker P, Hamer DH and Lazo JS (1988) Overexpression of metallothionein confers resistance to anticancer drugs. Science 241: 1813–1815
Kontozoglou TE, Banerjee D and Cherian MG (1989) Immunohistochemical localisation of metallothionein in human testicular embryonal adenocarcinoma. Virchows Arch 45: 545–549
Kouvidou CH, Stefanaki K, Dai Y, Tzardi M, Koutsoubi K, Darivianaki K, Karidi E, Rontogianni D, Zois E, Kakolyris S, Georgoulias V, Delides G and Kanavaros P (1997) P21/waf1 protein expression in nasopharyngeal carcinoma. Comparitive study with PCNA, P53 and MDM-2 protein expression. Anticancer Res 17: 2615–2620
Kuo SM, Kondo Y, DeFilippo JM, Ernstoff MS, Bahnson RR and Lazo JS (1994) Subcellular localization of metallothionein IIA in human bladder tumor cells using a novel epitope-specific antiserum. Toxicol Applied Pharmacol 125: 104–110
Lazo JS and Pitt BR (1995) Metallothionein and cell death by anticancer drugs. Annu Rev Pharmacol Toxicol 35: 635–653
Lo KW, Mok CH, Huang DP, Liu YX, Choi PH-K, Lee JCK and Tsao SW (1992) P53 mutation in human nasopharyngeal carcinomas. Anticancer Res 12: 1957–1964
McCormick CC and Lin LY (1991) Quantification and identification of metallothioneins by gel electrophoresis and silver staining. Meth Enzymol 205: 71–78
Meyn RE, Stephens LC and Milas L (1996) Programmed cell death and radioresistance. Cancer Metastasis Rev 15: 119–131
Oh Y and Mao L (1997) Biomarkers in head and neck carcinomas. Curr Opin Oncol 9: 247–256
Roychowdhury DF, Tseng A Jr, Fu KK, Weinberg V and Weidner N (1996) New prognostic factors in nasopharyngeal carcinoma. Cancer 77: 1419–1426
Schmid KW, Ellis IO, Gee JM, Darke BM, Lees WE, Kay J, Cryer A, Stark JM, Ofner D, Dunser M, Margreiter R, Daxenbichter G, Nicholson RI, Bier B, Bocker W and Jasani B (1993) Presence and possible significance of immunocytochemically demonstrable metallothionein overexpression in primary invasive ductal carcinoma of the breast. Virchows Arch 422: 153–159
Shanmugaratnam K, Chan SH, de-The G, Goh EH, Khor TH, Simons MJ and Tye CY (1979) Histopathology of nasopharyngeal carcinoma. Cancer 44: 1029–1044
Stirling JW and Graff PS (1995) Antigen unmasking for immunoelectron microscopy: labelling is improved by treating with sodium ethoxide or sodium metaperiodate, then heating on retrieval medium. J Histochem Cytochem 43: 115–123
Sundelin K, Jadner M, Norberg-Spaak L, Davidsson A and Hellquist HB (1997) Metallothionein and Fas (CD95) are expressed in squamous carcinoma of the tongue. Eur J Cancer 33: 1861–1864
Tan Y, Sinniah R, Bay B-H and Singh G (1999) Metallothionein expression and nuclear size in benign, borderline and malignant serous ovarian tumors. J Pathol 189: 60–65
Woo ES, Kondo Y, Watkins SC, Hoyt DG and Lazo JS (1996) Nucleophilic distribution of metallothionein in human tumor cells. Exp Cell Res 224: 365–371
Zhang X-H and Takenaka I (1998) Incidence of apoptosis and metallothionein expression in renal cell carcinoma. Br J Urol 81: 9–13
Zelger B, Hittmair A, Schir M, Ofner C, Ofner D, Fritsch PO, Bocker W, Jasani B and Schmid KW (1993) Immunohistochemically demonstrated metallothionein expression in malignant melanoma. Histopathology 23: 257–264
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Jayasurya, A., Bay, B., Yap, W. et al. Correlation of metallothionein expression with apoptosis in nasopharyngeal carcinoma. Br J Cancer 82, 1198–1203 (2000). https://doi.org/10.1054/bjoc.1999.1063
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DOI: https://doi.org/10.1054/bjoc.1999.1063
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