Specific methylation events contribute to the transcriptional repression of the mouse tissue inhibitor of metalloproteinases-3 gene in neoplastic cells

Citation
Wd. Pennie et al., Specific methylation events contribute to the transcriptional repression of the mouse tissue inhibitor of metalloproteinases-3 gene in neoplastic cells, CELL GROWTH, 10(4), 1999, pp. 279-286
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL GROWTH & DIFFERENTIATION
ISSN journal
1044-9523 → ACNP
Volume
10
Issue
4
Year of publication
1999
Pages
279 - 286
Database
ISI
SICI code
1044-9523(199904)10:4<279:SMECTT>2.0.ZU;2-2
Abstract
The tissue inhibitor of metalloproteinases-3 (TIMP-3) gene is specifically down-regulated in neoplastic cells of the mouse JB6 progression model, sugg esting a role for TIMP-3 inactivation in neoplastic progression. On the bas is of 5-azacytidine reversal, the mechanism for this down-regulation appear s to involve changes in the methylation state of the TIMP-3 promoter. Altho ugh total genomic methylation levels are comparable, specific differences i n the methylation of the TIMP-3 promoter were observed between preneoplasti c and neoplastic JB6 cells at three HpaII sites, with preneoplastic cells b eing less methylated. Expression of antisense methyltransferase in a neopla stic JB6 variant known to be hypermethylated in TIMP-3 resulted in reactiva tion of the endogenous TIMP-3 gene and restoration of hypomethylated status to the three implicated HpaII sites. Thus, hypermethylation at specific se quences in the TIMP-3 promoter appears to contribute to the silencing of th e gene in neoplastic cells.