TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma.
TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma.
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TFPI-2 是一种推定的肿瘤抑制基因，在鼻咽癌中经常因启动子高甲基化而失活
DOI：
10.1186/1471-2407-10-617
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发表时间：
2010-11-09
期刊：
影响因子：
3.8
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Wang S;Xiao X;Zhou X;Huang T;Du C;Yu N;Mo Y;Lin L;Zhang J;Ma N;Murata M;Huang G;Zhang Z
肿瘤抑制基因的表观遗传沉默在鼻咽癌（NPC）的肿瘤发生中起重要作用。组织因子途径抑制剂 - 2（TFPI - 2）是一种蛋白酶抑制剂。最近，TFPI - 2被认为是一种参与某些癌症的肿瘤发生和转移的肿瘤抑制基因。在本研究中，我们探讨了TFPI - 2在鼻咽癌中是否发生表观遗传失活。
通过逆转录聚合酶链反应（RT - PCR）评估TFPI - 2的转录表达水平。通过甲基化特异性PCR和亚硫酸氢盐基因组测序研究甲基化状态。通过将TFPI - 2表达重新引入鼻咽癌CNE2细胞系来探讨TFPI - 2作为鼻咽癌肿瘤抑制基因的作用。
TFPI - 2 mRNA转录在鼻咽癌CNE2细胞系中失活。TFPI - 2在66.7%（4/6）的鼻咽癌CNE2细胞系和88.6%（62/70）的鼻咽癌原发肿瘤中异常甲基化，但在正常鼻咽上皮中没有。去甲基化处理后，鼻咽癌CNE2细胞中的TFPI - 2表达可以恢复。TFPI - 2在鼻咽癌CNE2细胞中的异位表达诱导细胞凋亡，并抑制细胞增殖、集落形成和细胞迁移。
启动子高甲基化导致的TFPI - 2表观遗传失活在鼻咽癌中是一种常见且肿瘤特异性的事件。TFPI - 2可能被视为鼻咽癌中一种潜在的肿瘤抑制基因。
Epigenetic silencing of tumor suppressor genes play important roles in NPC tumorgenesis. Tissue factor pathway inhibitor-2 (TFPI-2), is a protease inhibitor. Recently, TFPI-2 was suggested to be a tumor suppressor gene involved in tumorigenesis and metastasis in some cancers. In this study, we investigated whether TFPI-2 was inactivated epigenetically in nasopharyngeal carcinoma (NPC). Transcriptional expression levels of TFPI-2 was evaluated by RT-PCR. Methylation status were investigated by methylation specific PCR and bisulfate genomic sequencing. The role of TFPI-2 as a tumor suppressor gene in NPC was addressed by re-introducing TFPI-2 expression into the NPC cell line CNE2. TFPI-2 mRNA transcription was inactivated in NPC cell lines. TFPI-2 was aberrantly methylated in 66.7% (4/6) NPC cell lines and 88.6% (62/70) of NPC primary tumors, but not in normal nasopharyngeal epithelia. TFPI-2 expression could be restored in NPC cells after demethylation treatment. Ectopic expression of TFPI-2 in NPC cells induced apoptosis and inhibited cell proliferation, colony formation and cell migration. Epigenetic inactivation of TFPI-2 by promoter hypermethylation is a frequent and tumor specific event in NPC. TFPI-2 might be considering as a putative tumor suppressor gene in NPC.
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影响因子：
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作者：
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通讯作者：
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