Liu X H, Wiley H S, Meikle A W
Department of Internal Medicine, University of Utah, Salt Lake City 84132.
J Clin Endocrinol Metab. 1993 Dec;77(6):1472-8. doi: 10.1210/jcem.77.6.8263129.
Androgens affect growth of the prostate gland and many prostate cancers. Androgens could mediate their mitogenic effects on prostate cells by an autocrine loop involving epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha that bind to the EGF/TGF-alpha receptor. We examined the effects of 5 alpha-dihydrotestosterone (DHT) and testosterone (T), EGF, and EGF-alpha on cell proliferation and 3H-thymidine incorporation in an androgen-dependent human prostate cancer cell line, ALVA101, in serum-free medium. The regulation of TGF-alpha and EGF/TGF-alpha receptor messenger RNA (mRNA) levels were determined by Northern blot analysis and EGF/TGF-alpha receptor protein by immunoblot. After 24 h of treatment of ALVA101 cells with DHT (10(-8) M) or T (10(-8) M), TGF-alpha mRNA levels increased 3- and 2.5-fold, respectively, and EGF/TGF-alpha receptor mRNA levels 2- and 1.5-fold, respectively. Cell numbers increased at day 5 in response to 10(-8) M DHT (18%, P < 0.01), 10(-8) M T (15%, P < 0.01), 20 ng/ml EGF (16%, P < 0.01), and 50 ng/mL TGF-alpha (34%, P < 0.01). DHT combined with TGF-alpha or T combined with EGF increased cell number 43% and 40% above control, respectively (P < 0.01 vs. DHT, P < 0.05 vs. TGF-alpha, T, EGF alone). The anti-EGF/TGF-alpha receptor antibody (528) blocked the cell proliferation induced by either DHT or TGF-alpha. We conclude that DHT and T stimulate synthesis of TGF-alpha and EGF/TGF-alpha receptor mRNAs and EGF/TGF-alpha receptor content in ALVA101 cells. This mitogenic effect of androgen on ALVA101 cells may involve TGF-alpha and the EGF/TGF-alpha receptor autocrine loop.
雄激素影响前列腺的生长以及许多前列腺癌。雄激素可通过涉及表皮生长因子（EGF）和转化生长因子（TGF）-α的自分泌环介导其对前列腺细胞的促有丝分裂作用，EGF和TGF-α可与EGF/TGF-α受体结合。我们在无血清培养基中检测了5α-双氢睾酮（DHT）、睾酮（T）、EGF和EGF-α对雄激素依赖的人前列腺癌细胞系ALVA101细胞增殖和3H-胸腺嘧啶核苷掺入的影响。通过Northern印迹分析确定TGF-α和EGF/TGF-α受体信使核糖核酸（mRNA）水平的调节，通过免疫印迹确定EGF/TGF-α受体蛋白。用DHT（10^(-8) M）或T（10^(-8) M）处理ALVA101细胞24小时后，TGF-α mRNA水平分别增加3倍和2.5倍，EGF/TGF-α受体mRNA水平分别增加2倍和1.5倍。在第5天，细胞数量因10^(-8) M DHT（增加18%，P < 0.01）、10^(-8) M T（增加15%；P < 0.01）、20 ng/ml EGF（增加16%，P < 0.01）和50 ng/mL TGF-α（增加34%，P < 0.01）而增加。DHT与TGF-α联合或T与EGF联合使细胞数量分别比对照增加43%和40%（与单独的DHT相比，P < 0.01；与单独的TGF-α、T、EGF相比；P < 0.05）抗EGF/TGF-α受体抗体（528）可阻断由DHT或TGF-α诱导细胞增殖。我们得出结论，DHT和T刺激ALVA101细胞中TGF-α和EGF/TGF-α受体mRNA的合成以及EGF/TGF-α受体含量。雄激素对ALVA101细胞的这种促有丝分裂作用可能涉及TGF-α和EGF/TGF-α受体自分泌环。
