DNA methylation analysis at distal and proximal promoter regions of the oestrogen receptor gene in breast cancers

Citation
H. Iwase et al., DNA methylation analysis at distal and proximal promoter regions of the oestrogen receptor gene in breast cancers, BR J CANC, 80(12), 1999, pp. 1982-1986
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
BRITISH JOURNAL OF CANCER
ISSN journal
0007-0920 → ACNP
Volume
80
Issue
12
Year of publication
1999
Pages
1982 - 1986
Database
ISI
SICI code
0007-0920(199908)80:12<1982:DMAADA>2.0.ZU;2-4
Abstract
Oestrogen receptor alpha (ER-alpha) gene has two specific promoters, distal (P0) and proximal (P1), which induce almost identical transcripts in size due to different splicing. We examined the methylation at both promoter reg ions of the ER-alpha gene using Hpall, a methylation-sensitive restriction enzyme, prior to polymerase chain reaction (PCR) amplification. To confirm the results of PCR-based methylation analysis, Southern hybridization was a lso performed. Twenty of 29 patients with ER-alpha-positive tumours and fiv e of 27 with ER-alpha-negative tumours were unmethylated at the P1 promoter region of the ER-alpha gene. The incidence of methylation was highly negat ively correlated with ER-alpha expression (P = 0.0002). A similarly negativ e correlation was observed at the P0 promoter region of the ER-alpha gene ( P = 0.0154). Additionally, the tumours with the ER-alpha gene hypermethylat ed at both promoter regions had definitely negative ER-alpha values. It was suggested that this epigenetic change might control ER-alpha expression, a nd might play an important role in the lass of hormone-dependence in breast cancer.