TRAF6 regulates proliferation of stromal cells in the transition and peripheral zones of benign prostatic hyperplasia via Akt/mTOR signaling

作者：Yunfeng Shi, Dian‐Jun Yu, Chenyi Jiang, Xing‐Jie Wang, Yiping Zhu, Ruizhe Zhao, Zhong Lv, Xiaowen Sun · 发表于：The Prostate · 年份：2017 · DOI：10.1002/pros.23456 · 被引用次数：21 · 研究领域：Urinary Bladder and Prostate Research、Prostate Cancer Treatment and Research、Pelvic floor disorders treatments

Background Increased prostatic smooth muscle tone and hyperplastic growth contribute to urethral obstruction and voiding symptoms in benign prostatic hyperplasia (BPH). It has been suggested that different proliferative potential of stromal cells between transition zone (TZ) and adjoining regions of the prostate plays a significant role in the development of BPH. However, the molecular mechanisms of this hyperplastic process remain unclear. We found tumor necrosis factor receptor‐associated factor 6 (TRAF6) highly expressed in TZ stromal cells compared to peripheral zone (PZ) stromal cells by gene array analyzes. Therefore, we aim to study the potential mechanisms of stromal TRAF6 in promoting BPH progression. Methods Stromal cells obtained from BPH‐derived primary cultures. The TRAF6‐siRNA vector were constructed and transfected into cultured human BPH primary TZ stromal cells, and TRAF6‐overexpressing vector were constructed and transfected into cultured human BPH primary PZ stromal cells. Stromal cells were recombined with BPH‐1 cells then subcutaneously inoculated into the kidney capsule of male nude mice. Cell proliferation was evaluated by CCK‐8 assay. Multiple proteins in the Akt/mTOR pathway were assessed using western blot. Results TRAF6 levels were increased in TZ stroma compared with PZ stroma of BPH. The in vitro cell culture and in vivo cell recombination revealed that selective downregulation of TRAF6 in TZ stromal cells led to suppression of the proliferation, ...