Methylation of estrogen and progesterone receptor gene 5' CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors.
Hormonal factors have a profound influence on the development, treatment, and outcome of breast cancer. The absence of steroid hormone receptors is highly correlated with resistance to antihormonal treatments. Work in cultured human breast cancer cell lines has shown that the absence of estrogen receptor (ER) gene expression in ER- cells is associated with extensive methylation of the ER gene 5' CpG island, and treatment with agents that demethylate the ER gene CpG island results in the production of functional ER protein. The current study shows that CpG islands in the 5' region of the ER and progesterone receptor (PR) genes are methylated in a significant fraction of primary human breast cancer tissues. The ER CpG island is methylated at the methylation-sensitive NotI restriction site in 9 of 39 (25%) of primary ER- breast cancers but remains unmethylated in 53 ER+ breast cancers and 9 normal breast specimens. Three methylation-sensitive restriction sites in the PR gene CpG island are not methylated in normal breast specimens and PR+ human breast cancers but are hypermethylated in 40% of PR- human breast tumors. These data demonstrate that methylation of the ER and PR gene CpG islands is associated with the lack of ER and PR gene expression in a significant fraction of human breast cancers.
Lapidus
R G
RG
The Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Ferguson
A T
AT
Ottaviano
Y L
YL
Parl
F F
FF
Smith
H S
HS
Weitzman
S A
SA
Baylin
S B
SB
Issa
J P
JP
Davidson
N E
NE
D001943:Breast Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D006801:Humans; D011960:Receptors, Estrogen / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D014407:Tumor Cells, Cultured
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone