Silencing of estrogen receptor alpha (ERalpha) gene by promoter hypermethylation is a frequent event in Chinese women with sporadic breast cancer.
Usually, the function of estrogen receptor alpha (ERalpha) could be silenced by ERalpha gene promoter hypermethylation. However, frequency of ERalpha promoter methylation and the clinicopathological characteristics of ERalpha methylation in Chinese women with sporadic breast cancer are unknown. The aim of this study was to determine the methylation status of ERalpha 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 ERalpha gene. In general, we found that ERalpha was methylated in 60.1% (83/138) tumors, including 57 of 69 ERalpha 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 ERalpha protein expression diminished with the frequency of ERalpha methylation (P < 0.0001, r = -0.469), the probability of methylation was increased for cases with ERalpha and PgR negativity (P < 0.00001). Our preliminary findings demonstrate, for what we believe to be the first time, that ERalpha methylation occurs in high frequency and is one of the mechanisms of ERalpha expression silence in a subset of sporadic breast cancers from Chinese women. Epigenetic alteration of the ERalpha gene may play an important role in the pathogenesis of breast cancer.
Zhao
Lin
L
Department of Pharmacology, China Medical University, Shenyang, Liaoning 110001, People's Republic of China.
Wang
Lin
L
Jin
Feng
F
Ma
Wenfeng
W
Ren
Jie
J
Wen
Xiaoyan
X
He
Miao
M
Sun
Mingli
M
Tang
Hongtao
H
Wei
Minjie
M
D044466:Asian People; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
D047628:Estrogen Receptor alpha