ArticleOncogene2003
Promoter methylation and silencing of the tissue factor pathway inhibitor-2 (TFPI-2), a gene encoding an inhibitor of matrix metalloproteinases in human glioma cells.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 80 citations in OpenAlex.
- Molecular regulators of thromboinflammation and angiogenesis in pediatric cancer: emerging roles of noncoding RNAs, epigenetics, and extracellular vesicles - narrative review.Annals of medicine and surgery (2012) · 2026Review
- MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer.Frontiers in epigenetics and epigenomics · 2026Review
- Olink Profiling of Intestinal Tissue Identifies Novel Biomarkers For Colorectal Cancer.Journal of proteome research · 2025Article
- Genetic studies of human-chimpanzee divergence using stem cell fusions.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- MeCP2 Epigenetic Silencing ofFrontiers in neuroscience · 2021Article
- A central role for MeCP2 in the epigenetic repression of miR-200c during epithelial-to-mesenchymal transition of glioma.Journal of experimental & clinical cancer research : CR · 2019Article
- Lysine‑specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI‑2.Molecular medicine reports · 2018Article
- MeCP2 level is associated with hepatocellular carcinoma development in chronic hepatitis B patients under antiviral therapy.International journal of clinical and experimental pathology · 2018Article
- Epigallocatechin gallate inhibits the growth and promotes the apoptosis of bladder cancer cells.Experimental and therapeutic medicine · 2017Article
- The CpG Dinucleotide Adjacent to a κB Site Affects NF-κB Function through Its Methylation.International journal of molecular sciences · 2017Article
- MeCP2 suppresses LIN28A expression via binding to its methylated-CpG islands in pancreatic cancer cells.Oncotarget · 2016Article
- Epigenetic silencing of methyl-CpG-binding protein 2 gene affects proliferation, invasion, migration, and apoptosis of human osteosarcoma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Promoter hypermethylation and silencing of tissue factor pathway inhibitor-2 in oral squamous cell carcinoma.Journal of translational medicine · 2014Article
- Hmga2 is required for canonical WNT signaling during lung development.BMC biology · 2014Article
- P14ARF suppresses tumor-induced thrombosis by regulating the tissue factor pathway.Cancer research · 2014Article
- Targeting of histone deacetylases in brain tumors.CNS oncology · 2013Review
- Deregulated chromatin remodeling in the pathobiology of brain tumors.Neuromolecular medicine · 2013Review
- Tissue factor pathway inhibitor-2 inhibits the growth and invasion of hepatocellular carcinoma cells and is inactivated in human hepatocellular carcinoma.Oncology letters · 2011Article
- TFPI-2 silencing increases tumour progression and promotes metalloproteinase 1 and 3 induction through tumour-stromal cell interactions.Journal of cellular and molecular medicine · 2011Article
- Co-localization of the oncogenic transcription factor MYCN and the DNA methyl binding protein MeCP2 at genomic sites in neuroblastoma.PloS one · 2011Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have shown previously that the tissue factor pathway inhibitor-2 (TFPI-2), a broad range proteinase inhibitor, is highly expressed in low-grade gliomas, but, minimally expressed or undetectable in glioblastomas, and that enforced expression of this gene reduces the invasive properties of brain tumor cells. Here, we examined the role of promoter methylation as a mechanism of TFPI-2 gene silencing. In SNB19 glioblastoma cells, which have no detectable TFPI-2 expression, 5-aza-2'-deoxycytidine (5aC), an inhibitor of DNA methyltransferase, induced TFPI-2 mRNA in a dose-dependent manner. Trichostatin A (TSA), the histone deacetylase (HDAC) inhibitor, by itself, was more efficient than 5aC in inducing TFPI-2 transcripts, and the 5aC+TSA combination resulted in highly synergistic reactivation of the gene, both at the transcript and protein levels. In Hs683 glioma cells, which express the TFPI-2 gene at high levels, transfection of the in vitro methylated TFPI-2 promoter constructs resulted in a drastic decrease of promoter activity compared to the unmethylated promoter. Further, the methylation-specific PCR in SNB19 and Hs683 cells showed that TFPI-2 gene repression was closely linked with methylation of the CpG islands in the promoter. Finally, the chromatin immunoprecipitation assays in SNB19 cells showed that the methylated and repressed TFPI-2 promoter was associated with the methyl-CpG binding protein 2 (MeCP2), and that gene reactivation resulted in the loss of MeCP2 from this site. These studies establish that TFPI-2 is transcriptionally silenced through promoter methylation in SNB19 cells.
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