METHYLATION OF THE ESTROGEN-RECEPTOR GENE CPG ISLAND MARKS LOSS OF ESTROGEN-RECEPTOR EXPRESSION IN HUMAN BREAST-CANCER CELLS

Breast cancer is the most common malignancy in women and hormone resis tance is a challenging problem in its treatment. Loss of estrogen rece ptor expression is an important means of hormone resistance, but the m echanisms involved are poorly understood. We now demonstrate a potenti al role for abnormal DNA methylation in transcriptional inactivation o f the estrogen receptor gene. Estrogen receptor-negative human breast cancer cells growing in culture lack estrogen receptor mRNA, have a hi gher capacity to methylate DNA, and display extensive methylation of t he CpG island in the 5' promoter region of the estrogen receptor gene, which would correlate with silencing of expression. These results sug gest that abnormal methylation could account for transcriptional inact ivation of the estrogen receptor gene and subsequent hormone resistanc e in some human breast cancers.