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Promoter hypermethylation may be an important mechanism of the transcriptional inactivation of ARRDC3, GATA5, and ELP3 in invasive ductal breast carcinoma

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Abstract

Hypermethylation of promoter CpG islands represents an alternative mechanism to inactivate tumor suppressor genes. This study was to detect promoter methylation status and mRNA expression levels of ARRDC3, ELP3, GATA5, and PAX6, and to explore the association between methylation and expression in invasive ductal carcinomas (IDCs) and matched normal tissues (MNTs) from breast cancer patients. Aberrant gene methylation was observed as follows: ARRDC3 in 38.5 %, ELP3 in 73.1 %, GATA5 in 48.1 %, and PAX6 in 50.0 % of IDCs. mRNA expression of ARRDC3, ELP3, and GATA5 in IDCs showed a lower level than that in MNTs (P < 0.001, P = 0.001 and P < 0.001, respectively). For ARRDC3, both methylated and unmethylated IDCs showed significantly lower expression values compared to MNTs (P = 0.001 and P = 0.007, respectively). For ELP3 and GATA5, methylated tumors only showed significantly lower expression values compared to MNTs (P = 0.001 and P < 0.001, respectively). For ARRDC3 and GATA5, methylation was associated with their less fold change in IDCs (P = 0.049 and P = 0.020, respectively). Methylation of ARRDC3 was significantly associated with grades and lymph node status of IDCs (P = 0.036 and P = 0.002, respectively). Methylation frequency of ELP3 was higher in lymph node positive versus lymph node negative tumors (P = 0.020); whereas methylation frequency of PAX6 was lower in tumors with the ER negative samples (P = 0.025). Our data suggested that promoter hypermethylation may be an important mechanism of the transcriptional inactivation of ARRDC3, GATA5, and ELP3 in IDCs.

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Acknowledgments

This study was supported by National Natural Science Foundation of China; Grant number: 81070452, National Research Foundation for Doctoral Program of Higher Education of China, Grant number: 20090181110048.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Preclinical and Forensic Medicine, Sichuan University, 3-17 Renmin South Road, Chengdu, 610041, Sichuan, People’s Republic of China

    Da Wang, Jin Chen, Xian-Yao Zhou, Qiu-Jun Liu & Chang-Long Li

  2. Department of Thyroid and Breast Surgery, West China Hospital, Sichuan University, 3-17 Renmin South Road, Chengdu, 610041, Sichuan, People’s Republic of China

    Hong-Jiang Li

  3. Key Laboratory of Bio-Resources and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, No. 24 South Section 1, Yihuan Road, Chengdu, 610065, Sichuan, People’s Republic of China

    Peng-Na Yang

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  1. Da Wang
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Wang, D., Yang, PN., Chen, J. et al. Promoter hypermethylation may be an important mechanism of the transcriptional inactivation of ARRDC3, GATA5, and ELP3 in invasive ductal breast carcinoma. Mol Cell Biochem 396, 67–77 (2014). https://doi.org/10.1007/s11010-014-2143-y

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