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

• Published in: BMC cancer Vol. 10; no. 1; p. 617
• Main Authors: Wang, Shumin, Xiao, Xue, Zhou, Xiaoying, Huang, Tingting, Du, Chunping, Yu, Nana, Mo, Yingxi, Lin, Longde, Zhang, Jinyan, Ma, Ning, Murata, Mariko, Huang, Guangwu, Zhang, Zhe
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09-11-2010; BioMed Central; BMC
• Subjects: Azacitidine - analogs & derivatives; Azacitidine - pharmacology; Carcinoma - genetics; Carcinoma - metabolism; Cell Line, Tumor; Cell Proliferation; Development and progression; DNA Methylation; Epigenesis, Genetic; Epigenetics; Flow Cytometry - methods; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene therapy; Genes, Tumor Suppressor; Genetic aspects; Glycoproteins - metabolism; Hospitals; Humans; Identification and classification; Lung cancer; Medical research; Medicin och hälsovetenskap; Methylation; Mineral oils; Nasopharyngeal cancer; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - metabolism; Otolaryngology; Physiological aspects; Promoter Regions, Genetic; Proteins; RNA, Messenger - metabolism; Science; Studies; Tumor suppressor genes; China
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-10-617

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.