Protein arginine N-methyltransferase 2 reverses tamoxifen resistance in breast cancer cells through suppression of ER-α36

Shen,Yingying; Zhong,Jing; Liu,Jianghua; Liu,Kehuang; Zhao,Jun; Xu,Ting; Zeng,Ting; Li,Zhimei; Chen,Yajun; Ding,Wenjun; Wen,Gebo; Zu,Xuyu; Cao,Renxian

doi:10.3892/or.2018.6350

Protein arginine N-methyltransferase 2 reverses tamoxifen resistance in breast cancer cells through suppression of ER-α36

Authors:
- Yingying Shen
- Jing Zhong
- Jianghua Liu
- Kehuang Liu
- Jun Zhao
- Ting Xu
- Ting Zeng
- Zhimei Li
- Yajun Chen
- Wenjun Ding
- Gebo Wen
- Xuyu Zu
- Renxian Cao
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Affiliations: Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China, Department of Metabolism and Endocrinology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: April 2, 2018 https://doi.org/10.3892/or.2018.6350
Pages: 2604-2612
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is one of the most common malignancies in females, and 17β-estradiol (E2)/estrogen receptor α (ERα) signaling plays an important role in the initiation and progression of breast cancer. The role of the ER-α subtype and its co-regulator in the initiation of breast cancer and the occurrence of tamoxifen resistance remains to be further elucidated. In our previous studies, protein arginine N-methyltransferase 2 (PRMT2), a co-regulator of estrogen receptor-α (ER-α), was confirmed to interact with ER-α66 and has the ability to inhibit cell proliferation in breast cancer cells. In the present study, we found that tamoxifen treatment induced a decrease in PRMT2 and an increase in ER-α36 as well as ER-α36-mediated non-genomic effect in MDA-MB-231 cells, which were relatively resistant to tamoxifen by contrast to MCF-7 cells. Moreover, PRMT2 was able to interact with ER-α36 directly, suppress ER-α36 and downstream PI3K/Akt and MAPK/ERK signaling, reversing the tamoxifen resistance of breast cancer cells. The present study may be meaningful for understanding the role of PRMT2 in breast cancer progression and for developing a new endocrine therapeutic strategy for breast cancer patients with tamoxifen resistance.

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