Hennenberg Martin, Schreiber Andrea, Ciotkowska Anna, Rutz Beata, Waidelich Raphaela, Strittmatter Frank, Stief Christian G, Gratzke Christian
Department of Urology, Ludwig-Maximilians University, Munich, Germany.
Department of Urology, Ludwig-Maximilians University, Munich, Germany.
Life Sci. 2015 Feb 15;123:18-24. doi: 10.1016/j.lfs.2014.12.006. Epub 2014 Dec 18.
Stromal growth is critical for prostate enlargement during benign prostatic hyperplasia (BPH). While responses of prostate cells to single growth factors have been well characterized, responses to multiple growth factors at once are poorly understood. Here, we examined the effects of combinations between epidermal growth factor (EGF), fibroblast growth factor (FGF), and transforming growth factor-β1 (TGF-β1) in human prostate stromal cells.
EGF, FGF, and TGF-β1 were applied to WPMY-1 cells, an immortalized, non-malignant line of stromal cells from the human prostate. Hypertrophic responses were assessed by protein/DNA ratio, and cyclin D1 mRNA by RT-PCR. Expression of EGF, FGF, and TGF-β1 and their receptors in human prostate tissue was analyzed by RT-PCR, Western blot, and fluorescence staining.
Hypertrophic responses to single growth factors and combinations were similar. Combinations showed additive effects on cyclin D1 mRNA. Combination of EGF with TGF-β1, but not EGF or TGF-β1 alone, caused assembly of cells to a new two-dimensional structure, being characterized by dense aggregates connected by branches of few cells. EGF and TGF-β1 were detected together in human prostates. Receptors for EGF and TGF-β colocalized on stromal cells in human prostates.
Responses of prostate stromal cells to combinations of EGF, FGF, and TGF-β1 may be quantitatively different, qualitatively different, or similar to responses to single growth factors. The combination of EGF and TGF-β1, but not EGF or TGF-β1 alone, induces aggregation of prostate stromal cells, which may be relevant for morphogenesis.
在良性前列腺增生（BPH）过程中，基质生长对前列腺增大至关重要。虽然前列腺细胞对单一生长因子的反应已得到充分表征，但对多种生长因子同时存在时的反应却知之甚少。在此，我们研究了表皮生长因子（EGF）、成纤维细胞生长因子（FGF）和转化生长因子-β1（TGF-β1）联合作用于人前列腺基质细胞的效果。
将EGF、FGF和TGF-β1应用于WPMY-1细胞，这是一种源自人前列腺的永生化、非恶性基质细胞系。通过蛋白质/DNA比值评估肥大反应，并通过逆转录聚合酶链反应（RT-PCR）检测细胞周期蛋白D1 mRNA。通过RT-PCR、蛋白质免疫印迹法和荧光染色分析人前列腺组织中EGF、FGF和TGF-β1及其受体的表达。
对单一生长因子及其组合的肥大反应相似。组合对细胞周期蛋白D1 mRNA有累加效应。EGF与TGF-β1的组合而非单独的EGF或TGF-β1，导致细胞组装成一种新的二维结构，其特征是由少数细胞分支连接的密集聚集体。在人前列腺中同时检测到EGF和TGF-β1。EGF和TGF-β的受体在人前列腺基质细胞上共定位。
前列腺基质细胞对EGF、FGF和TGF-β1组合的反应在数量上可能不同、质量上可能不同，或者与对单一生长因子的反应相似。EGF和TGF-β1的组合而非单独的EGF或TGF-β1，诱导前列腺基质细胞聚集，这可能与形态发生有关。
