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Correlation between the germline methylation status in ERβ promoter and the risk in prostate cancer: a prospective study

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Abstract

Familial aggregation of cancer may reflect an overall contribution of inherited genes or a shared mechanism for the manipulation of gene function. DNA methylation in the promoter regions is considered to be a mechanism through which tumor suppressor genes are inhibited, which will lead to tumorigenesis and tumor progression. To evaluate the association between the methylation status in the promoter of estrogen receptor (ER) β,possibly a tumor suppressor gene specific for prostate cancer, and the risk in prostate cancer in a Chinese population, a case–control study that included 56 sporadic prostate cancer cases and 60 healthy controls was conducted. Genomic DNA was extracted from peripheral blood of all the subjects for analyzing the methylation status of the ERβ promoter by methylation-specific PCR, which was verified by bisulfite genomic sequencing PCR. A significant difference was observed in the methylation frequencies of the ERβ promoter between cancer patients (12/56, 21.4 %) and healthy controls (5/60, 8.3 %). Prostate cancer (PC-3 and DU-145) and prostatic epithelial (RWPE-1) cell lines were treated with various concentrations of the methyltransferase inhibitor 5-Aza-2′-dC. Expression of ERβ was detected at both transcriptional and translational levels. As a result, both mRNA and protein of ERβ were elevated following treatment with increasing concentrations of the demethylating agent. Taken together, our results support the conclusion that abnormal methylation of the ERβ promoter may increase genetic susceptibility to prostate cancer.

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Acknowledgments

We received considerable technical assistance for this study from Feng Ying and Jiang Wu. We would like to thank Yang Hu, Yu Chen, Xueting Wang, Fangfang Sun, Huiming Zhu, Cong Wang, Chaowen Shi, Mingming Yuan and Ruoyu Wang for their helpful assistance. This work was supported by National Natural Science Foundation of China (21377052, 81572512, 31370524, 81570059), Natural Science Foundation of Jiangsu Province of China (BK20131281, BK20151398).

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Authors and Affiliations

  1. Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, 210093, Jiangsu, China

    Lihui Wang, Xiannan Meng, Xiang Chen, Xiaoqian Lin, Ye Liu, Xiaodong Han & Dongmei Li

  2. Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, Jiangsu, China

    Lihui Wang, Xiannan Meng, Xiang Chen, Xiaoqian Lin, Ye Liu, Xiaodong Han & Dongmei Li

  3. Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China

    Pan Zhang & Weidong Gan

  4. Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Institute of Biomedicine, University of Gothenburg, 40530, Gothenburg, Sweden

    Zou Xiang

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  1. Lihui Wang
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Correspondence to Weidong Gan, Xiaodong Han or Dongmei Li.

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Supplementary Fig. 1

Relative mRNA expression of estrogen receptor β in peripheral blood of prostate cancer patients (n = 56) and healthy controls (n = 60). mRNA was extracted from peripheral blood samples and estrogen receptor β expression was determined by RT-qPCR. Data are shown as mean ± SD (TIFF 13798 kb)

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Wang, L., Zhang, P., Meng, X. et al. Correlation between the germline methylation status in ERβ promoter and the risk in prostate cancer: a prospective study. Familial Cancer 15, 309–315 (2016). https://doi.org/10.1007/s10689-015-9850-8

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