Usually, the function of estrogen receptor alpha (ERα) could be silenced by ERα gene promoter hypermethylation. However, frequency of ERα promoter methylation and the clinicopathological characteristics of ERα methylation in Chinese women with sporadic breast cancer are unknown. The aim of this study was to determine the methylation status of ERα promoter and its possible correlation with clinicopathological features in a series of 138 sporadic breast cancers in Chinese women. ER1, ER3, ER4, and ER5 primers were used for methylation-specific polymerase chain reaction (MSP) to analyze the CpG methylation of promoter region of ERα gene. In general, we found that ERα was methylated in 60.1% (83/138) tumors, including 57 of 69 ERα negative tumors (82.6%, P < 0.00001). Specifically within each region the methylation percentage of ER1, ER3, ER4 and ER5 were 34.8%, 35.5%, 39.1%, and 36.9% respectively. The degree of methylation at four CpG sites was higher in breast cancer compared with benign breast hyperplasia (P < 0.00001). In addition, the levels of ERα protein expression diminished with the frequency of ERα methylation (P < 0.0001, r = −0.469), the probability of methylation was increased for cases with ERα and PgR negativity (P < 0.00001). Our preliminary findings demonstrate, for what we believe to be the first time, that ERα methylation occurs in high frequency and is one of the mechanisms of ERα expression silence in a subset of sporadic breast cancers from Chinese women. Epigenetic alteration of the ERα gene may play an important role in the pathogenesis of breast cancer.
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M. Wei is supported by Fund of Ministry of Education of China (No. 20050159020).
L. Zhao and L. Wang have contributed equally to this work.
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Zhao, L., Wang, L., Jin, F. et al. Silencing of estrogen receptor α (ERα) gene by promoter hypermethylation is a frequent event in Chinese women with sporadic breast cancer. Breast Cancer Res Treat 117, 253–259 (2009). https://doi.org/10.1007/s10549-008-0192-1