Methylation of TFPI-2 gene is not the sole cause of its silencing.

Journal Article

TFPI-2 (tissue factor pathway inhibitor-2) is a serine protease inhibitor that may suppress tumor cell invasion and metastasis. TFPI-2 expression is often lost in cells derived from tumors of diverse organs. We have examined whether aberrant hypermethylation of the 5' end of the TFPI-2 gene is associated with its loss of expression. After 5-azacytidine treatment of three cell lines lacking TFPI-2 expression (HT1080 fibrosarcoma cells, MCF-7 breast carcinoma cells, and LNCaP prostate carcinoma cells), TFPI-2 transcripts could be detected by RT-PCR. In these three cell lines, methylation of the 5' end of the TFPI-2 gene was detected, while two prostate carcinoma cell lines in which the TFPI-2 gene was expressed, PC-3 and DU-145, showed no methylation. However, all the three cell lines which lacked TFPI-2 expression also contained unmethylated TFPI-2 alleles. Furthermore, a transiently transfected TFPI-2 promoter was non-functional in the three cell lines, but function was attained following treatment with 5-azacytidine. Our results indicate that while methylation of the TFPI-2 gene is associated with its silencing, it is not the sole cause, and we suggest that one or more components of pathways regulating TFPI-2 expression have also undergone methylation-associated silencing in these cell lines.

Full Text

Duke Authors

Cited Authors

  • Rao, CN; Segawa, T; Navari, JR; Xu, L; Srivastava, S; Moul, JW; Phillips, B

Published Date

  • April 2003

Published In

Volume / Issue

  • 22 / 4

Start / End Page

  • 843 - 848

PubMed ID

  • 12632077

International Standard Serial Number (ISSN)

  • 1019-6439

Language

  • eng

Conference Location

  • Greece