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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.

Publication ,  Journal Article
Konduri, SD; Srivenugopal, KS; Yanamandra, N; Dinh, DH; Olivero, WC; Gujrati, M; Foster, DC; Kisiel, W; Ali-Osman, F; Kondraganti, S; Lakka, SS ...
Published in: Oncogene
July 17, 2003

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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Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

July 17, 2003

Volume

22

Issue

29

Start / End Page

4509 / 4516

Location

England

Related Subject Headings

  • Repressor Proteins
  • Promoter Regions, Genetic
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Methyl-CpG-Binding Protein 2
  • Hydroxamic Acids
  • Humans
  • Histone Deacetylases
  • Histone Deacetylase Inhibitors
  • Glycoproteins
 

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Konduri, S. D., Srivenugopal, K. S., Yanamandra, N., Dinh, D. H., Olivero, W. C., Gujrati, M., … Rao, J. S. (2003). 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. Oncogene, 22(29), 4509–4516. https://doi.org/10.1038/sj.onc.1206695
Konduri, Santhi D., Kalkunte S. Srivenugopal, Niranjan Yanamandra, Dzung H. Dinh, William C. Olivero, Meena Gujrati, Donald C. Foster, et al. “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.Oncogene 22, no. 29 (July 17, 2003): 4509–16. https://doi.org/10.1038/sj.onc.1206695.
Konduri SD, Srivenugopal KS, Yanamandra N, Dinh DH, Olivero WC, Gujrati M, et al. 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. Oncogene. 2003 Jul 17;22(29):4509–16.
Konduri, Santhi D., et al. “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.Oncogene, vol. 22, no. 29, July 2003, pp. 4509–16. Pubmed, doi:10.1038/sj.onc.1206695.
Konduri SD, Srivenugopal KS, Yanamandra N, Dinh DH, Olivero WC, Gujrati M, Foster DC, Kisiel W, Ali-Osman F, Kondraganti S, Lakka SS, Rao JS. 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. Oncogene. 2003 Jul 17;22(29):4509–4516.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

July 17, 2003

Volume

22

Issue

29

Start / End Page

4509 / 4516

Location

England

Related Subject Headings

  • Repressor Proteins
  • Promoter Regions, Genetic
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Methyl-CpG-Binding Protein 2
  • Hydroxamic Acids
  • Humans
  • Histone Deacetylases
  • Histone Deacetylase Inhibitors
  • Glycoproteins