Differential expression of metallothionein isoforms in nasopharyngeal cancer and inhibition of cell growth by antisense down-regulation of metallothionein-2A.
Biological functions of metallothionein (MT) proteins which are encoded by 10 functional MT isoforms, include cell proliferation, differentiation and apoptosis. The aim of this study was to compare the relative expression levels of functional MT mRNA isoforms in three nasopharyngeal cancer (NPC) cell lines with laryngeal carcinoma and embryonic lung cell lines by quantitative real-time RT-PCR. All the NPC lines exhibited expression of the MT-2A transcript, whereas the MT-1E isoform was expressed in well differentiated HK1 and moderately differentiated TW01 but not in poorly differentiated CNE2 cells. Interestingly, TW01 and HEp-2 laryngeal cancer cells exhibited similar expression profiles with both MT-1E and MT-2A isoforms being detected at levels below those of MRC-5 embryonic lung fibroblasts. Functional studies of the MT-2A isoform by down-regulating expression of this gene with MT-2A antisense oligonucleotide in CNE2 cells, showed a reduction in cell viability and proliferation. These findings may provide valuable information in the search for novel therapeutic strategies against NPC.
Tan
Owen June-Keong
OJ
Department of Microbiology, National University of Singapore, Kent Ridge 117597, Singapore.
Bay
Boon-Huat
BH
Chow
Vincent Tak-Kwong
VT
D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation; D006131:Growth Inhibitors / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D008668:Metallothionein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; C491053:MT2A protein, human; D020319:Oligodeoxyribonucleotides, Antisense; D020033:Protein Isoforms; D012333:RNA, Messenger; D008668:Metallothionein