V. Martin et al., INVOLVEMENT OF DNA METHYLATION IN THE CONTROL OF THE EXPRESSION OF ANESTROGEN-INDUCED BREAST-CANCER-ASSOCIATED PROTEIN (PS2) IN HUMAN BREAST CANCERS, Journal of cellular biochemistry, 65(1), 1997, pp. 95-106
pS2 gene has been used to investigate the relationship between alterat
ions of DNA methylation patterns in human tumors and gene expression.
The expression of pS2, which is transcriptionally controlled by estrog
ens in breast cancer cell lines, is restricted to estrogen-receptor-ri
ch human breast tumors. We found that the CCGG site within the promote
r/enhancer sequence of pS2 was hypomethylated in estrogen-receptor-ric
h breast tumors expressing this gene. The amount of DNA molecules unme
thylated at this site was related to the amount of pS2 mRNA detected i
n the samples. The demethylation of this region, which contains the es
trogen responsive element, was confirmed by genomic sequencing. Transi
ent expression of functional human estrogen receptors stimulated the e
xpression of the endogenous pS2 in HeLa cells, but failed, in BT-20 ce
lls, to stimulate expression of this gene. Since the promoter/enhancer
region of pS2 is unmethylated in HeLa cells and methylated in BT-20 c
ells, these data also support the hypothesis that DNA methylation migh
t be involved in the control of pS2 expression. (C) 1997 Wiley-Liss, I
nc.