Correlation of metallothionein expression with apoptosis in nasopharyngeal carcinoma

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

Regulation of the H19 imprinting gene expression in human nasopharyngeal carcinoma by methylation

“…28 Furthermore, metallothionein I also plays a protective role against DNA damage and apoptosis induced by oxidative or external stress and has been postulated to contribute to radiation resistance in tumor cells. 29 Other genes that were also differentially upregulated in HK1 cells include the MMP-10 gene, genes encoding MCP-3, CPR2, CDK inhibitor 2A and IGF binding protein 3 (BP-3) (Fig. 1b, Table I).…”

Metallothionein 1E mRNA is highly expressed in oestrogen receptor-negative human invasive ductal breast cancer

“…It is possible that MT-1E may participate in that role. MTs are known to influence tumour growth and survival by promoting cell proliferation and cellular repair processes, enhancing resistance to chemotherapy and inhibiting apoptosis (Kagi 1991;Kondo et al, 1995;Abdel-Mageed and Agrawal, 1997;Jayasurya et al, 2000). High MT expression has also been reported to be associated with aggressive behaviour in endometrial carcinoma (McCluggage et al, 1999).…”

“…MTs are known to play putative roles in cancer cell proliferation and apoptosis (Abdel-Mageed and Agrawal, 1997;Jayasurya et al, 2000) as well as in resistance to radiation and chemotherapeutic agents (Lohrer and Robson, 1989;Yang et al, 1994, Kondo et al, 1995. In breast cancer, MT overexpression has been well documented by immunohistochemical analysis (Schmid et al, 1993;Fresno et al, 1993;Haerslev et al, 1995;Goulding et al, 1995;Jin et al, 1999), and shown to be predominantly associated with poor prognosis.…”

Prognostic Significance of Glutathione S-Transferase-Pi in Invasive Breast Cancer

“…For the detection of apoptosis in tissue sections, DNA fragmentation was identified using the terminal deoxynucleotidyl transferase-mediated, dUTPbiotin nick end-labeling (TUNEL) technique with the commercially available TdT-FragELTM DNA Fragmentation Detection kit (Oncogene Research Products) (16) in 113 tumor sections. After deparaffinization and rehydration, slides were permeabilized in 20 mg/mL of proteinase K. Endogenous peroxidase was inactivated by treating with 3% hydrogen peroxide.…”