TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma.
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.
Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, PR China.
Shumin
S
Wang
Xue
X
Xiao
Xiaoying
X
Zhou
Tingting
T
Huang
Chunping
C
Du
Nana
N
Yu
Yingxi
Y
Mo
Longde
L
Lin
Jinyan
J
Zhang
Ning
N
Ma
Mariko
M
Murata
Guangwu
G
Huang
Zhe
Z
Zhang
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
D006023:Glycoproteins; D012333:RNA, Messenger; C021240:tissue-factor-pathway inhibitor 2; D000077209:Decitabine; D001374:Azacitidine