The correlation between DNMT1 and ERα expression and the methylation status of ERα, and its clinical significance in breast cancer
نویسندگان
چکیده
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.
منابع مشابه
Effect of Silibinin on Maspin and ERα Gene Expression in MCF-7 Human Breast Cancer Cell Line
Background and objective: According to reports, a serine protease inhibitor (Maspin) suppresses metastasis, invasion and angiogenesis in breast and prostate cancers. Silibinin is a natural polyphenolic flavonoid with anti-cancer activity. We assessed the effects of silibinin on cell viability, maspin and ERα gene expression in MCF-7 cell line. <s...
متن کاملERα propelled aberrant global DNA hypermethylation by activating the DNMT1 gene to enhance anticancer drug resistance in human breast cancer cells
Drug-induced aberrant DNA methylation is the first identified epigenetic marker involved in chemotherapy resistance. Understanding how the aberrant DNA methylation is acquired would impact cancer treatment in theory and practice. In this study we systematically investigated whether and how ERα propelled aberrant global DNA hypermethylation in the context of breast cancer drug resistance. Our da...
متن کاملmicroRNA-152 Mediates DNMT1-Regulated DNA Methylation in the Estrogen Receptor α Gene
BACKGROUND Estrogen receptor α (ERα) has been shown to protect against atherosclerosis. Methylation of the ERα gene can reduce ERα expression leading to a higher risk for cardiovascular disease. Recently, microRNAs have been found to regulate DNA methyltransferases (DNMTs) and thus control methylation status in several genes. We first searched for microRNAs involved in DNMT-associated DNA methy...
متن کاملPromoter Hypermethylation of Estrogen Receptor Alpha Gene Is Correlated to Estrogen Receptor Negativity in Iranian Patients with Sporadic Breast Cancer
OBJECTIVE Breast Cancer is the most common cancer in Iranian women. Breast tumors are classified based on the estrogen receptor alpha (ERα) expression status into ER negative and ER positive tumors. ER negative tumors tend to have worse prognosis and less likely to respond to endocrine therapy. Aberrant methylation of gene promoter is one of the mechanisms for gene silencing in breast tumors. B...
متن کاملArsenic trioxide re-sensitizes ERα-negative breast cancer cells to endocrine therapy by restoring ERα expression in vitro and in vivo.
Approximately one-third of breast cancers lack estrogen receptor α (ERα) because of the hypermethylation of the CpG island in the receptor's promoter. These tumors are associated with poorer histological differentiation, a higher growth fraction, are rarely responsive to endocrine therapy and have a worse clinical outcome. Thus, re-expression of ERα in ERα-negative breast cancers may restore th...
متن کامل