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Androgen and AR contribute to breast cancer development and metastasis: an insight of mechanisms

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Abstract

The role of androgen and androgen receptor (AR) in breast carcinogenesis has long been a disputed issue. This report provides a mechanistic insight into how androgen and AR contributes to invasion and metastasis of breast cancer. We find that dihydrotestosterone (DHT) is able to induce the epithelial-to-mesenchymal transition in breast cancer cells in an AR-dependent/estrogen receptor-independent manner. This process is dependent on the demethylation activity of lysine-specific demethylase 1A (LSD1) by epigenetically regulating the target genes E-cadherin and vimentin. In vivo, DHT promotes metastasis in a nude mouse model, and AR and LSD1 are indispensable in this process. We establish that higher expression of nucleus AR to cytoplasm AR associated with worse prognostic outcomes in breast cancer patient samples. This study maps an ‘androgen-AR/LSD1-target genes’ pathway in breast carcinogenesis, implicating the importance of hormonal balance in women, and the potential clinical significance of serum androgen and AR in prediction of breast cancer and selection of breast cancer therapy.

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Acknowledgements

We thank Dr Wei Huang from School of Mathematics and Statistics of Northeast Normal University for kindly providing statistical analysis guidance. This work was supported by the grants from the National Natural Science Foundation of China (Grant numbers 31570718, 31571478, 31571317 and 31371294), and a grant from The University S & T Innovation Platform of Jilin Province for Economic Fungi (#2014B-1).

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Authors and Affiliations

  1. The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun, China

    J Feng, L Li, J Liu, Y Zhang & B Huang

  2. Department of Bone and Soft Tissue Tumors, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

    L Li

  3. The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China

    N Zhang, X Li & J Lu

  4. Department of Pathology, The Second Hospital of Jilin University, Changchun, China

    L Zhang & H Gao

  5. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China

    G Wang & Y Li

  6. School of Science, Auckland University of Technology, Auckland, New Zealand

    D Liu

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Feng, J., Li, L., Zhang, N. et al. Androgen and AR contribute to breast cancer development and metastasis: an insight of mechanisms. Oncogene 36, 2775–2790 (2017). https://doi.org/10.1038/onc.2016.432

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