Transcriptional Silencing of the TFPI-2 Gene by Promoter Hypermethylation in Choriocarcinoma Cells
- 15 January 2003
- journal article
- Published by Walter de Gruyter GmbH in Biological Chemistry
- Vol. 384 (7) , 1029-34
- https://doi.org/10.1515/bc.2003.115
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.Keywords
This publication has 18 references indexed in Scilit:
- Demonstration of a Tissue Factor Pathway Inhibitor 2 Messenger RNA Synthesis by Pure Villous Cytotrophoblast Cells Isolated from Term Human Placentas1Biology of Reproduction, 2003
- Characterization and functional analysis of TFPI-2 gene promoter in a human choriocarcinoma cell lineThrombosis Research, 2003
- CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter futureOncogene, 2002
- 5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapyOncogene, 2002
- Demonstration of inducible TFPI-2 mRNA synthesis in BeWo and JEG-3 trophoblast cells using a competitive RT-PCRThrombosis Research, 2002
- Expression of Serine Proteinase Inhibitor PP5/TFPI-2/MSPI Decreases the Invasive Potential of Human Choriocarcinoma Cells in Vitro and in VivoGynecologic Oncology, 2001
- Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosisJournal of Clinical Investigation, 2001
- Role of tissue factor pathway inhibitor-2 (TFPI-2) in amelanotic melanoma (C-32) invasion.Clinical & Experimental Metastasis, 2000
- MinireviewBiological Chemistry, 1998
- A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands.Proceedings of the National Academy of Sciences, 1992