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
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.