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Open Access Highly Accessed Research article

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

Shumin Wang1, Xue Xiao1, Xiaoying Zhou1, Tingting Huang1, Chunping Du1, Nana Yu1, Yingxi Mo2, Longde Lin1, Jinyan Zhang1, Ning Ma3, Mariko Murata2, Guangwu Huang1 and Zhe Zhang1*

Author Affiliations

1 Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, PR China

2 Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Japan

3 Faculty of Health Science, Suzuka University of Medical Science, Japan

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BMC Cancer 2010, 10:617  doi:10.1186/1471-2407-10-617

Published: 9 November 2010

Abstract

Background

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).

Methods

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.

Results

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.

Conclusions

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.