TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma

BMC Cancer

Research Article

Yingxi Mo¹  Mariko Murata¹  Jinyan Zhang²  Guangwu Huang²  Xue Xiao²  Chunping Du²  Zhe Zhang²  Shumin Wang²  Tingting Huang²  Nana Yu²  Xiaoying Zhou²  Longde Lin²  Ning Ma³ 

[1] Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Japan;Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China;Faculty of Health Science, Suzuka University of Medical Science, Japan;

关键词: Promoter Hypermethylation;    Bisulphite;    CNE2 Cell;    Normal Nasopharyngeal Epithelium;    Bisulphite Genomic Sequencing;   

DOI  :  10.1186/1471-2407-10-617

 received in 2010-06-15, accepted in 2010-11-09,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundEpigenetic 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).MethodsTranscriptional 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.ResultsTFPI-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.ConclusionsEpigenetic 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.

【 授权许可】

Unknown   
© Wang et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.