Department of Pathology, The Norwegian Radium Hospital, Institute of Clinical Medicine, Oslo University Hospital, Faculty of Medicine, University of Oslo, Oslo, Norway.
PLoS One. 2013 Jul 30;8(7):e70558. doi: 10.1371/journal.pone.0070558. Print 2013.
Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG) was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression.
雄激素在前列腺癌的发展中起着至关重要的作用。然而，目前尚不清楚雄激素是否会影响前列腺癌的干细胞样特性，而这种特性对前列腺癌的进展很重要。在这项研究中，我们表明，在体外 DHT 处理后，前列腺癌细胞系 LNCaP 和 PC-3 表现出更高的克隆形成能力和更高水平的干细胞相关因子 CD44、CD90、Oct3/4 和 Nanog 的表达。此外，这些细胞中的性激素结合球蛋白 (SHBG) 也同时被上调。当用 SHBG siRNA 敲低阻断 SHBG 基因时，DHT 诱导的 Oct3/4、Nanog、CD44 和 CD90 的表达也在这些细胞中被相应阻断。临床样本的免疫组织化学评估显示，良性前列腺组织中 SHBG 表达呈弱阳性和阴性区域，而大多数前列腺癌呈强阳性。此外，较高的 SHBG 表达水平与较高的 Gleason 评分、更多的精囊侵犯和淋巴结转移显著相关。总之，我们的研究结果表明，SHBG 在体外 DHT 暴露时上调前列腺癌细胞的干性，并且前列腺癌样本中的 SHBG 表达与不良的临床病理特征显著相关，表明 SHBG 在前列腺癌进展中的作用。
