Zhang Zhisong, Duan Lei, Du Xiaoling, Ma Hongshun, Park Irwin, Lee Chung, Zhang Ju, Shi Jiandang
Department of Biochemistry and Molecular Biology, College of Life Sciences, Nankai University, Tianjin, China.
Prostate. 2008 Apr 1;68(5):508-16. doi: 10.1002/pros.20722.
Estrogen is involved in the development and progression of benign prostatic hyperplasia (BPH). It can stimulate proliferation of prostate stromal cells (PrSCs). However, the exact mechanism remains unclear.
We used the primary cultured human PrSCs and a prostate stromal cell line, WPMY-1, to examine the signaling pathways involved in estrogen-mediated proliferation of PrSCs. Cells were treated with 17beta-estradiol (E(2)) or BSA-E(2). Cell proliferation was assessed by the MTT assay and by cell counting. Western blot analysis was used to determine the status of activation of ERK1/2.
Results indicated that both E(2) and BSA-E(2) stimulated proliferation of primary PrSCs and WPMY-1 cells. ERK was rapidly activated by E(2) and BSA-E(2). PD98059, which is a selective ERK inhibitor, significantly inhibited estrogen-induced cell proliferation. PrSCs expressed estrogen receptor alpha (ERalpha) and GPR30 but not ERbeta. Small hairpin RNA (shRNA) to ERalpha, but not to GPR30, blocked estrogen-mediated ERK activation and cell proliferation.
The results indicated that estrogen could activate ERK pathway through the non-genomic ERalpha pathway, leading to proliferation of PrSCs.
雌激素参与良性前列腺增生（BPH）的发生和发展。它可刺激前列腺基质细胞（PrSCs）增殖。然而，确切机制仍不清楚。
我们使用原代培养的人PrSCs和前列腺基质细胞系WPMY-1，来研究雌激素介导的PrSCs增殖所涉及的信号通路。细胞用17β-雌二醇（E₂）或牛血清白蛋白-E₂（BSA-E₂）处理。通过MTT法和细胞计数评估细胞增殖。采用蛋白质印迹分析来确定ERK1/2的激活状态。
结果表明，E₂和BSA-E₂均刺激原代PrSCs和WPMY-1细胞增殖。E₂和BSA-E₂可快速激活ERK。PD98059是一种选择性ERK抑制剂，可显著抑制雌激素诱导的细胞增殖。PrSCs表达雌激素受体α（ERα）和GPR30，但不表达ERβ。针对ERα而非GPR30的小发夹RNA（shRNA）可阻断雌激素介导的ERK激活和细胞增殖。
结果表明，雌激素可通过非基因组ERα途径激活ERK通路，导致PrSCs增殖。
