Transcriptional Silencing of the TFPI-2 Gene by Promoter Hypermethylation in Choriocarcinoma Cells

Florent Hubé (1) , Pascale Reverdiau (2) , S Iochmann (3) , Jérome Rollin (4) , Catherine Cherpi-Antar (5) , Yves Gruel (6)

1 EDC - Centre épigénétique et destin cellulaire
2 PRPA - Pathologies Respiratoires : Protéolyse et Aérosolthérapie
3 UT - Université de Tours
4 LEFG - Laboratoire d'Exploration Fonctionnelle des Génomes
5 iBraiN - Imaging, Brain & Neuropsychiatry
6 GICC UMR 6239 CNRS - Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011]

Tissue factor pathway inhibitor-2 (TFPI-2), a Kunitztype 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.

Mots clés: Tissue factor pathway inhibitor 2; Transcriptional silencing; 5’-Aza-2’-deoxycytidine; JAR cells; Methylation status; Normal trophoblast cells

Domaines: Cancer; Génomique, Transcriptomique et Protéomique [q-bio.GN]

Florent Hubé, Pascale Reverdiau, S Iochmann, Jérome Rollin, Catherine Cherpi-Antar, et al.. Transcriptional Silencing of the TFPI-2 Gene by Promoter Hypermethylation in Choriocarcinoma Cells. Biological Chemistry, 2003, 384 (7), pp.1029-1034. ⟨10.1515/BC.2003.115⟩. ⟨hal-02127398⟩