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Nuclear loss of protein arginine N-methyltransferase 2 in breast carcinoma is associated with tumor grade and overexpression of cyclin D1 protein

Oncogene volume 33, pages 5546–5558 (2014)Cite this article

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Abstract

Human protein arginine N-methyltransferase 2 (PRMT2, HRMT1L1) is a protein that belongs to the arginine methyltransferase family, and it has diverse roles in transcriptional regulation through different mechanisms depending on its binding partners. In this study, we provide evidences for the negative effect of PRMT2 on breast cancer cell proliferation in vitro and in vivo. Morever, cyclin D1, one of the key modulators of cell cycle, was found to be downregulated by PRMT2, and PRMT2 was further shown to suppress the estrogen receptor α-binding affinity to the activator protein-1 (AP-1) site in cyclin D1 promoter through indirect binding with AP-1 site, resulting in the inhibition of cyclin D1 promoter activity in MCF-7 cells. Furthermore, a positive correlation between the expression of PRMT2 and cyclin D1 was confirmed in the breast cancer tissues by using tissue microarray assay. In addition, PRMT2 was found to show a high absent percentage in breast caner cell nuclei and the nuclear loss ratio of PRMT2 was demonstrated to positively correlate with cyclin D1 expression and the increasing tumor grade of invasive ductal carcinoma. Those results offer an essential insight into the effect of PRMT2 on breast carcinogenesis, and PRMT2 nuclear loss might be an important biological marker for the diagnosis of breast cancer.

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Acknowledgements

This work is supported by projects from the National Natural Science Foundation of P.R.China (Grant No. 31200573, 81272906, 81272355 and 81172542), Hunan Provincial Natural Science Foundation of China (12JJ3116) and The Education Department of Hunan Province Youth Fund (12B108).

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  1. J Zhong and R-X Cao: The first two authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Clinical Medicine, First Affiliated Hospital of University of South China, Hengyang, PR China

    J Zhong, R-X Cao, J-H Liu, Y-B Liu, J Wang, L-P Liu, Y-J Chen, J Yang, Q-H Zhang, Y Wu, W-J Ding, T Hong, X-H Xiao, X-Y Zu & G-B Wen

  2. Department of Metabolism and Endocrinology, First Affiliated Hospital of University of South China, Hengyang, PR China

    R-X Cao, J-H Liu, J Yang, T Hong & X-H Xiao

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Zhong, J., Cao, RX., Liu, JH. et al. Nuclear loss of protein arginine N-methyltransferase 2 in breast carcinoma is associated with tumor grade and overexpression of cyclin D1 protein. Oncogene 33, 5546–5558 (2014). https://doi.org/10.1038/onc.2013.500

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