Hypermethylation of estrogen receptor-α gene in atheromatosis patients and its correlation with homocysteine

Huang, Yuguang; Zhi, Yanfang; Wang, Shuren

doi:10.1016/j.pathophys.2009.02.010

Cited by 46 publications

(39 citation statements)

References 20 publications

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“…The results may lead to speculation as to the potential relationship between BRCA1 and hormonal signaling in familial BC. In the present study, a negative correlation between ERα methylation and ERα expression was found in the familial BC patients (coefficient correlation r= −0.322; p=0.001), which was in agreement with previous results that the increased methylation level of the CpG islands within the ERα promoter region is highly negatively associated with ERα expression in a variety of diseases including neoplastic and atherosclerotic lesions [29,30]. Zhao et al [13] suggested that downregulation of ERα expression through promoter methylation is highly prevalent in sporadic BC.…”

Section: Discussionsupporting

confidence: 93%

Promoter methylation status and expression of estrogen receptor alpha in familial breast cancer patients

et al. 2011

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The hypermethylation of estrogen receptor alpha (ERα) promoter is a common molecular alteration in sporadic breast cancer (BC), but its involvement in familial BC remains largely unknown. In the present study, we analyzed the methylation statuses of four regions (ER1, ER3, ER4, and ER5) of the ERα promoter and the ERα expression levels of 113 familial BC patients in a Han Chinese Population from northeastern China and evaluated the association between major clinicopathological features and the hypermethylation statuses of the ERα gene. Tumor samples were analyzed for ERα methylation status by the methylation-specific polymerase chain reaction for ERα, PR, p53, BRCA-1, and BRCA-2 by immunohistochemical (IHC) staining and for Her-2 status by IHC and fluorescence in situ hybridization (FISH). ERα methylation was observed in tumor tissues in 47/113 (41.6%) familial BC patients. There were no significant differences in the methylation statuses among ER1 (20.4%), ER3 (18.6%), ER4 (17.7%), and ER5 (19.5%; χ (2) = 3.89, p > 0.05). An association between ERα expression level and its promoter methylation level was found. In addition, ERα methylation was significantly correlated with tumor size, PR expression, p53 nuclear accumulation, and BRCA-1 and BRCA-2 statuses. In conclusion, in familial BC patients, the level of ERα gene promoter methylation correlates with ERα expression, PR, p53 nuclear accumulation, and BRCA-1 and BRCA-2 statuses. Epigenetic alteration of ERα gene may play an important role in the pathogenesis of familial BC.

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Section: Discussionsupporting

confidence: 93%

Promoter methylation status and expression of estrogen receptor alpha in familial breast cancer patients

et al. 2011

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“…Many studies have tried to access its gene profiling to clinical application. Accumulating evidences have indicated that an increased methylation level of the CpG islands within the ERα promoter region is highly negatively associated with ER expression in a variety of diseases including neoplastic and atherosclerotic lesions [33][34][35][36]. In our research, CpG islands of ERα methylation in sporadic BLBC subtype were significantly frequent compared to sporadic non-BLBC.…”

Section: Discussionsupporting

confidence: 47%

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

Jing

Mao

et al. 2011

Tumor Biol.

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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.

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“…Hyperhomocysteinemia is also a risk factor for cardiovascular, neurological, and psychiatric diseases; osteoporotic fractures; and complications during pregnancy (Herrmann, 2006). Furthermore, its epigenetic perturbing feature that causes DNA hypomethylation (James et al, 2002;Jamaluddin et al, 2007;Obeid et al, 2007) or hypermethylation (Lenz et al, 2006;Huang et al, 2009) is receiving increasing attention. In this study, homocysteine enhanced the methylation levels of cytosine in day 6 morulae compared with the no-additive control (Fig.…”

Section: -Methylcytosinementioning

confidence: 99%

Expression of methylation pathway enzymes in bovine oocytes and preimplantation embryos

et al. 2010

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The methylation pathway, which consists of two metabolic cycles of nutrients, i.e., the methionine and folate cycles, generates S-adenosylmethionine, the methyl donor for the methylation of DNA and histones. Using reverse transcription-polymerase chain reaction, we examined the gene expression patterns of the methylation pathway enzymes during bovine oocyte maturation and preimplantation embryonic development up to the blastocyst stage. Bovine oocytes were demonstrated to have the mRNA of all methylation pathway enzymes examined, namely, methionine adenosyltransferase 1A (MAT1A), MAT2A, MAT2B, S-adenosylhomocysteine hydrolase (AHCY), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), betaine-homocysteine methyltransferase (BHMT), serine hydroxymethyltransferase 1 (SHMT1), SHMT2, and 5,10-methylenetetrahydrofolate reductase (MTHFR). All the transcripts were consistently expressed throughout all developmental stages, except for MAT1A, which was not detected from the 8-cell stage onward and BHMT, which was not detected in the 8-cell stage. Immunofluorescence analysis of MAT1A protein revealed the relatively higher expression in oocytes and early cleavage stage embryos up to the 8-cell stage compared with the morula and blastocyst stage. Further, to investigate the effects of methylation pathway disruption during the earliest stages of embryonic development, the effects of exogenous homocysteine on preimplantation development and DNA methylation of bovine embryos were investigated in vitro. As results, high concentrations of homocysteine induced hypermethylation of genomic DNA as well as developmental retardation in bovine embryos. These results provide a new insight into nutrient-sensitive epigenetic regulation and perturbation at the earliest stage of our life.

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Hypermethylation of estrogen receptor-α gene in atheromatosis patients and its correlation with homocysteine

Cited by 46 publications

References 20 publications

Promoter methylation status and expression of estrogen receptor alpha in familial breast cancer patients

Promoter methylation status and expression of estrogen receptor alpha in familial breast cancer patients

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

Expression of methylation pathway enzymes in bovine oocytes and preimplantation embryos

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