The correlation between DNMT1 and ERα expression and the methylation status of ERα, and its clinical significance in breast cancer.

Abstract

The correlation between the expression of DNA methyltransferase-1 (DNMT1) and estrogen receptor α (ERα), as well as the methylation status of ERα, was analyzed to investigate the clinical significance of DNMT1 and ERα in breast cancer. Substance P immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) were utilized to detect the protein and mRNA expression levels of DNMT1 and ERα in 112 breast cancer and 20 normal breast specimens. Methylation specific PCR was utilized to detect the methylation status of ERα in ERα-positive and -negative breast cancer specimens and 20 normal breast specimens. The results of the present study revealed that DNMT1 protein and mRNA levels were low in normal breast specimens (10.00 and 46.05%, respectively) and ERα-positive breast cancer specimens (15.00 and 48.68%, respectively), compared with increased levels in ERα-negative breast cancer specimens (81.11 and 88.89%, respectively; P<0.05). The methylation rate of ERα was highest in ERα-negative breast cancer specimens (86.11%) compared with normal breast specimens and ERα-positive breast cancer specimens (10.00 and 36.84%, respectively; P<0.05). Positive expression of ERα protein was observed to be associated with progesterone receptor expression (P<0.05), however, no such association was observed for age, menopause state, tumor size, number of positive nodes, Tumor-Node-Metastasis stage or tumor type (P>0.05). The protein and mRNA expression levels of DNMT1 were negatively correlated with ERα expression (P<0.05). DNMT1 expression was positively correlated with methylation of ERα (P<0.05), and was positively correlated with the methylation of CpG islands of ERα, indicating that the detection of DNMT1 expression may be significant for the diagnosis and typing of breast cancer.