Abstract
The methylation of the human oestrogen receptor (ER) gene was analysed by restriction enzymes in normal and neoplastic human breast tissues and cell lines. CCGG sequences in regions inside the gene, which are methylated both in normal breast and in tissues that are not the target of the oestrogen, are hypomethylated in 30% of tumours, both ER+ and ER- carcinomas. Moreover, 5' sequences of the gene, which are hypomethylated in normal breast and not in tissues not the target of oestrogen, are methylated to a lower degree in ER+ carcinomas, whereas they are methylated to a greater degree in ER- carcinomas. However, the same region is equally hypomethylated in both ER+ and ER- cancer cell lines. Our results indicate that in breast carcinomas ER DNA methylation is deranged, and in cancer cell lines is different from that observed in primary tumours. Furthermore, the abnormal methylation in the 5' end seems to be related to abnormal expression, namely diffuse hypomethylation in carcinomas with high ER content and hypermethylation in carcinomas without ER. These findings support our previous hypothesis that DNA methylation could be involved in the control of ER gene expression and demonstrate that abnormal ER gene methylation is a typical feature of breast cancers.
Highlights
We have recently reported an inverse correlation between the extent of methylation and the expression of the ER gene in normal human tissues (Piva et al, 1989a)
Taken together the results indicate that some CCGG sites located inside the ER gene are rarely hypomethylated in breast carcinomas, but always in breast cell lines, independently of their ER content
A similar pattern was found in carcinomatous and normal endometrium which always showed the lowest degree of methylation of the ER gene. These results indicate that Ml, M13 and M14 CCGG sites were hypomethylated in the majority of ER + carcinomas and demethylated in cell lines, whereas they were methylated in the majority of ER - carcinomas
Summary
We have recently reported an inverse correlation between the extent of methylation and the expression of the ER gene in normal human tissues (Piva et al, 1989a). The 5' region of the gene is demethylated in normal endometrium, which contains high ER levels, and strongly methylated in white blood cells, which do not contain ER. A DNA region, internal to the gene and usually methylated in normal endometrium, is consistently hypomethylated in endometrial carcinomas, in association with a fall of ER gene expression (Piva et al, 1989b). It is unclear whether the decrease in expression of the ER gene is related to the abnormal hypomethylation or whether this hypomethylation is an invariable property of specific tumours
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