| Nasopharyngeal carcinoma (NPC) is a rare disease in most parts of the world but is one of the most prevalent malignant tumors and the leading cause of death among all head and neck cancers in Southern China. Compared with the incidence of DNA mutation and deletion, inactivation of tumor suppressor genes (TSG) plays an important role in NPC. It has been shown that aberrant DNA methylation of CpG islands is an important mechanism for epigenetic inactivation of TSGs.To identify novel candidate tumor suppressor genes silenced by DNA hypermethylation in NPC, in our previous study, we analyzed the global expression restoration in the NPC cell lines-CNE2 and HONE1, after the treatment with 5-aza-dC and TSA by performing a genome-wide screening. TFPI-2(tissue factor pathway inhibitor-2) was up-regulated 107 and 49 folds respectively after the treatment. Thus, TFPI-2 might be a target gene with expression suppressed by promoter hypermethylation in NPC.In this study, we confirm our results by RT-PCR, methylation specific PCR. Our data showed that TFPI-2 expression was down-regulated in NPC cell lines and primary tumors compared with normal nasopharyngeal epithelia. Promoter methylation of TFPI-2 could be observed in 66.7% (4/6) of the NPC cell lines and 88.6% (62/70) of primary tumors, but not in any of the normal epithelia. Loss of TFPI-2 expression can be greatly restored by the methyltransferase inhibitor 5-aza-dC in NPC cell lines. Ectopic expression of TFPI-2 in TFPI-2-silenced and-methylated NPC cell line CNE2 shows that TFPI-2 can inhibit colony formation and cell migration, induce the cell apoptosis, which provided further evidence that TFPI-2 might possess properties as a candidate tumor suppressor gene in NPC. The present work demonstrated that epigenetic inactivation of TFPI-2 by promoter hypermethylation is a frequent and tumor specific event in NPC and TFPI-2 might be considering as a putative tumor suppressor gene in NPC.
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