Research Center of Urology and Andrology, Zhongnan Hospital, Wuhan University, Wuhan, China.
Cell Biochem Funct. 2011 Mar;29(2):120-5. doi: 10.1002/cbf.1731. Epub 2011 Feb 2.
Estradiol (E₂) and its receptor estrogen receptor alpha (ERα) are implicated in the pathology of stromal-predominant benign prostatic hyperplasia (BPH). Insulin-like growth factor 1(IGF1) is produced primarily by stromal cells in the prostate. Recent study showed that E₂-mediated regulation of IGF1 in mouse uterus requires the DNA binding ability of ERα. However, the crosstalk between ERα and IGF1 in the prostate has not been addressed yet. Therefore, in this study we employed mouse prostatic smooth muscle cells (PSMCs) as a model to demonstrate that E₂ stimulated the proliferation of PSMCs and up-regulated the expression of IGF1 and its receptor IGF1R as well as cyclin D1 in PSMCs, all of which could be inhibited by shRNA-mediated knockdown of ERα. Furthermore, we found that exogenous IGF1 could not promote cell proliferation and cyclin D1 expression in PSMCs subjected to shRNA-mediated knockdown of ERα. Interestingly, blockage of IGF1R by antibody could inhibit E₂-stimulated PSMCs proliferation. Altogether our present study provides the first line of evidence that there is crosstalk between ERα and IGF1 signaling in PSMCs proliferation in which ERα up-regulates the expression of IGF1 and IGF1R, and IGF1 signaling is indispensable to mediate downstream effects of E₂ and ERα.
雌二醇（E₂）及其受体雌激素受体α（ERα）与基质占主导的良性前列腺增生（BPH）的病理学有关。胰岛素样生长因子 1（IGF1）主要由前列腺中的基质细胞产生。最近的研究表明，E₂在小鼠子宫中对 IGF1 的调节需要 ERα 的 DNA 结合能力。然而，ERα 和 IGF1 在前列腺中的串扰尚未得到解决。因此，在这项研究中，我们使用小鼠前列腺平滑肌细胞（PSMCs）作为模型，证明 E₂刺激 PSMCs 的增殖，并上调 IGF1 及其受体 IGF1R 和细胞周期蛋白 D1 在 PSMCs 中的表达，所有这些都可以通过 shRNA 介导的 ERα 敲低来抑制。此外，我们发现外源性 IGF1 不能促进 ERα 介导的 shRNA 敲低的 PSMCs 中的细胞增殖和细胞周期蛋白 D1 表达。有趣的是，抗体阻断 IGF1R 可抑制 E₂刺激的 PSMCs 增殖。总之，我们的这项研究首次提供了证据表明，ERα 和 IGF1 信号通路在 PSMCs 增殖中存在串扰，其中 ERα 上调 IGF1 和 IGF1R 的表达，而 IGF1 信号通路对于介导 E₂ 和 ERα 的下游效应是不可或缺的。
