前列腺癌
癌症研究
前列腺
雄激素剥夺疗法
雄激素受体
医学
内科学
癌症
化学
癌细胞
雄激素
下调和上调
细胞生长
生物
内分泌学
基因
激素
生物化学
作者
Lei Chen,Yue-Yang Wang,Li Deng,Cheng Wang,Shiyuan Wang,Sihui Shao,Zhengyang Zhu,Jing Zhao,Yu Zhang,Yuan Ruan,Bangmin Han,Shujie Xia,Chenyi Jiang,Fu-Jun Zhao
标识
DOI:10.1016/j.canlet.2021.01.017
摘要
The androgen receptor (AR) is expressed in prostate fibroblasts in addition to normal prostate epithelial cells and prostate cancer (PCa) cells. Moreover, AR activation in fibroblasts dramatically influences prostate cancer (PCa) cell behavior. Androgen deprivation leads to deregulation of AR downstream target genes in both fibroblasts and PCa cells. Here, we identified LIM domain only 2 (LMO2) as an AR target gene in prostate fibroblasts using ChIP-seq and revealed that LMO2 can be repressed directly by AR through binding to androgen response elements (AREs), which results in LMO2 overexpression after AR deactivation due to normal prostate fibroblasts to cancer-associated fibroblasts (CAFs) transformation or androgen deprivation therapy. Next, we investigated the mechanisms of LMO2 overexpression in fibroblasts and the role of this event in non-cell-autonomous promotion of PCa cells growth in the androgen-independent manner through paracrine release of IL-11 and FGF-9. Collectively, our data suggest that AR deactivation deregulates LMO2 expression in prostate fibroblasts, which induces castration resistance in PCa cells non-cell-autonomously through IL-11 and FGF-9.
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