Estrogen receptor-alpha promoter methylation in sporadic basal-like breast cancer of Chinese women

Abstract

Basal-like breast cancer (BLBC) appears to be characterized by a relatively unfavorable prognosis and lack of a specific therapeutic target. Estrogen receptor-alpha (ERα) has been widely accepted as a prognostic marker and a predictor for endocrine therapy response of breast cancer. This study aimed to clarify the correlation of ERα methylation with the pathogenesis and clinicopathological significance of sporadic BLBC of Chinese women without a family history of the cancer. The methylation of ERα promoter was investigated in genomic DNA of 60 sporadic BLBC with 108 cases of non-BLBC as control by methylation-specific polymerase chain reaction. We also investigated the expression of p53, breast cancer gene (BRCA)-1, and BRCA-2 by immunohistochemistry and analyzed the correlation between ERα methylation and clinicopathological features of BLBC. ERα methylation was observed in 48 of 60 (80.0%) sporadic BLBC, which was significantly higher than in sporadic non-BLBC cancer (47/108, 43.5%; χ2=20.89, p<0.01). No correlation was found between the ERα methylation and age and menopausal status, while it was significantly associated with lymph node metastasis, tumor stage, nuclear p53 accumulation, and BRCA-1 and BRCA-2 expression in sporadic BLBC. The ERα methylation status in basal-like breast cancer was significantly higher than in sporadic non-basal-like breast cancer. It was associated with the lymph node metastasis, tumor stage, p53 nuclear accumulation, and BRCA-1 and BRCA-2 expression in BLBC. It may play an important role in BLBC pathogenesis.

Immune Landscape of Breast Cancers

“…Epigenetic reprogramming that affects cancer cell-viability, migration, apoptosis, and gene expression can be induced by the over-production of bacterial metabolite by-products [ 55 , 56 ], through which they also gain resistance to antibiotics. This reprogramming has also been implicated in breast cancer subtype development, where the promoters of genes, such as ER α in TNBC [ 57 ] and BRCA1, have been found to be hyper-methylated [ 53 ].…”

Estrogen receptor-α promoter methylation is a biomarker for outcome prediction of cisplatin resistance in triple-negative breast cancer

“…Previous results indicated that ERα methylation was associated with tumor stage, lymph node metastasis, nuclear accumulation of p53 and BRCA1 expression in basal-like breast cancer ( 14 , 34 – 37 ). The mechanism of action of cisplatin in breast cancer cells with DNA repair dysfunctions remains unknown.…”

“…For samples with 2 µg DNA, salmon sperm DNA (Sigma Aldrich; Merck KgaA, Darmstadt, Germany) was added as carrier prior to modification. A total of 30 µl of 10 mM hydroquinone (Sigma Aldrich; Merck KGaA) and 3 M sodium bisulfite (Sigma Aldrich; Merck KGaA) at pH 5 were added and mixed, and samples were incubated under mineral oil at 50°C for 16 h. ERα1, ERα3, ERα4 and ERα5 for MSP using the six primer pairs as described previously ( 14 ) and purified using the Promega Wizard Genomic DNA Purification kit (A1120, Promega Corporation, Madison, WI, USA). The positive control consisted of alleles from healthy volunteers methylated with SssI methyltransferase (New England Biolabs, Inc., Ipswich, MA, USA), and the negative control was modified using RNA-free water.…”

“…Methylation of the ERα promoter has previously been demonstrated to be associated with sporadic TNBC, ranging between 30 and 40% in breast cancer samples. It has been demonstrated that methylation of the ERα1, ERα3, ERα4 or ERα5 promoters is associated with basal-like breast cancer ( 14 ). ERα and BRCA1 promoter methylation may contribute to poor disease-free survival (DFS) and overall survival (OS) times.…”

Expression pattern and methylation of estrogen receptor α in breast intraductal proliferative lesions

“…We selected ER1, ER3, ER4 and ER5 for MSP from the six primer pairs previously described ( 8 , 9 ) because these covered the most significant methylated loci. The oligonucleotides of primers were synthesized by Sangon Biotech Co., Ltd. (Shanghai, China).…”