Androgen and AR contribute to breast cancer development and metastasis: an insight of mechanisms
Androgen and AR contribute to breast cancer development and metastasis: an insight of mechanisms
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雄激素和 AR 有助于乳腺癌的发展和转移：机制的见解。
DOI：
10.1038/onc.2016.432
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发表时间：
2017-05-18
期刊：
影响因子：
8
通讯作者：
Huang, B.
中科院分区：
文献类型：
--
作者：
Feng, J.;Li, L.;Huang, B.
雄激素和雄激素受体（AR）在乳腺癌发生中的作用一直是一个有争议的问题。本报告提供了雄激素和AR如何有助于乳腺癌的侵袭和转移的机制的见解。我们发现，双氢睾酮（DHT）能够诱导乳腺癌细胞的上皮间质转化在AR依赖/雌激素受体非依赖的方式。该过程依赖于赖氨酸特异性脱甲基酶1A（LSD 1）的脱甲基活性，通过表观遗传学调节靶基因E-钙粘蛋白和波形蛋白。在体内，DHT在裸鼠模型中促进转移，AR和LSD 1在此过程中不可或缺。我们确定，在乳腺癌患者样本中，细胞核AR相对于细胞质AR的更高表达与更差的预后结果相关。本研究绘制了乳腺癌发生中的“雄激素-AR/LSD 1-靶基因”通路，暗示了女性激素平衡的重要性，以及血清雄激素和AR在乳腺癌预测和乳腺癌治疗选择中的潜在临床意义。
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.