Transcriptional silencing of the TFPI-2 gene by promoter hypermethylation in choriocarcinoma cells.
Biol Chem
; 384(7): 1029-34, 2003 Jul.
Article
em En
| MEDLINE
| ID: mdl-12956419
ABSTRACT
Tissue factor pathway inhibitor-2 (TFPI-2), a Kunitz-type serine proteinase inhibitor associated with the extracellular matrix, has been shown to reduce tumor invasion. In the present study we identified the presence of a complete CpG island region spanning exon 1 and the three transcription initiation sites. We demonstrate that DNA demethylation by 5'-aza-2'-deoxycytidine restores TFPI-2 transcription in JAR choriocarcinoma cells. The effect of in vitro DNA methylation on TFPI-2 promoter function was also confirmed with TFPI-2/luciferase promoter constructs. Finally, we determined the precise methylation status of CpG sites of the TFPI-2 promoter in normal and tumor trophoblast cells using the bisulfite genomic sequencing method. We conclude that hypermethylation of the TFPI-2 gene is correlated with transcriptional silencing and that the TFPI-2 gene may be a candidate tumor suppressor gene.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas
/
Regiões Promotoras Genéticas
/
Metilação de DNA
/
Inativação Gênica
/
Inibidores Enzimáticos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article