Gerdes M J, Dang T D, Larsen M, Rowley D R
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Endocrinology. 1998 Aug;139(8):3569-77. doi: 10.1210/endo.139.8.6138.
Stromal-epithelial interactions in the prostate gland are dependent on androgen regulation of prostate stromal cells, yet little is known about androgen action in these cell types. Recent reports have demonstrated that androgen-regulated gene transcription can be stimulated or inhibited by certain growth factors, indicating cross-talk mechanisms. To address potential cross-talk in signaling pathways between androgen and transforming growth factor-beta1 (TGFbeta1) in prostate stromal cells, the PS-1 prostate smooth muscle cell line was examined. In the presence of physiological concentrations of androgen, PS-1 cell proliferation was stimulated, and androgen receptor (AR) exhibited a nuclear localization pattern. The addition of TGFbeta1 (25 pM) was capable of blocking androgen-induced proliferation, but had no direct effect in cultures without androgen. Immunocytochemistry to localize AR subcellular distribution showed that TGFbeta1 (5-100 pM) altered the distribution of AR from the nucleus to the cytoplasm. Other growth factors, including fibroblast growth factor-2, epidermal growth factor, and TGFbeta2 had no effect on AR distribution. The TGFbeta1-induced nuclear to cytoplasmic change in receptor localization was rapid (initiated within 30 min), was neutralized by TGFbeta1 antibodies, did not require new protein synthesis, and was complete by 6 h. Removal of TGFbeta1 from the culture medium resulted in a rapid redistribution of AR to the nucleus, indicating reversible mechanisms. Northern analysis of the ddp17 marker transcript for androgen action in PS-1 cells showed that androgen-stimulated ddp17 expression was inhibited in the presence of TGFbeta1 (25 pM). TGFbeta1 induced a similar nuclear to cytoplasmic distribution of AR in primary cultures of rat prostate stromal cells. TGFbeta1, however, had no effect on AR distribution in either the LNCaP prostatic carcinoma cell line or the DDT1MF-2 leiomyosarcoma cell line. Specific cross-talk between TGFbeta1 and AR signaling pathways in prostate stromal cells may play a significant role in prostate development and stromal cell response in carcinoma progression.
前列腺中的基质 - 上皮相互作用依赖于雄激素对前列腺基质细胞的调节，但对于雄激素在这些细胞类型中的作用了解甚少。最近的报道表明，某些生长因子可刺激或抑制雄激素调节的基因转录，这表明存在相互作用机制。为了研究前列腺基质细胞中雄激素与转化生长因子 - β1（TGFβ1）信号通路之间潜在的相互作用，对PS - 1前列腺平滑肌细胞系进行了检测。在生理浓度雄激素存在的情况下，PS - 1细胞增殖受到刺激，并且雄激素受体（AR）呈现核定位模式。添加TGFβ1（25 pM）能够阻断雄激素诱导的增殖，但在无雄激素的培养物中没有直接作用。通过免疫细胞化学定位AR亚细胞分布表明，TGFβ1（5 - 100 pM）可使AR的分布从细胞核转移至细胞质。其他生长因子，包括成纤维细胞生长因子 - 2、表皮生长因子和TGFβ2对AR分布没有影响。TGFβ1诱导的受体定位从细胞核到细胞质的变化迅速（在30分钟内开始），可被TGFβ1抗体中和，不需要新的蛋白质合成，并且在6小时内完成。从培养基中去除TGFβ1会导致AR迅速重新分布到细胞核，表明存在可逆机制。对PS - 1细胞中雄激素作用的ddp17标记转录本进行Northern分析表明，在TGFβ1（25 pM）存在的情况下，雄激素刺激的ddp17表达受到抑制。TGFβ1在大鼠前列腺基质细胞原代培养物中诱导了类似的AR从细胞核到细胞质的分布。然而，TGFβ1对LNCaP前列腺癌细胞系或DDT1MF - 2平滑肌肉瘤细胞系中的AR分布均无影响。前列腺基质细胞中TGFβ1与AR信号通路之间的特异性相互作用可能在前列腺发育和癌进展中的基质细胞反应中起重要作用。
