Greenebaum Cancer Center, University of Maryland School of Medicine, 655 West Baltimore Street, BRB 9-029, Baltimore, MD 21201, U.S.A.
Anticancer Res. 2011 Oct;31(10):3129-35.
Therapies that inhibit androgen receptor (AR) are needed for treatment of castration-resistant prostate cancer (CRPC). The ErbB3 binding protein 1 (EBP1) reduces protein expression of both AR and its target genes in CRPC. Although EBP1 regulates AR in hormone-sensitive prostate cancer cells, by both destabilizing AR mRNA and inhibiting protein translation, the mechanism of EBP1 down regulation of AR in CRPC is unknown.
Western blot and quantitative PCR analysis of cell lysates and polysomes were used to assess AR mRNA, protein expression and translation.
In contrast to hormone- dependent cells, EBP1 did not change steady state levels of AR mRNA or AR mRNA stability in hormone refractory cells. EBP1 did slow protein translation of AR mRNA. The ErbB3/4 ligand heregulin further diminished AR translation in EBP1 -transfected cells, but not in control cells.
These studies suggest that one pathway of EBP1 down-regulation of AR levels may be lost in CRPC.
对于去势抵抗性前列腺癌（CRPC）的治疗，需要抑制雄激素受体（AR）的疗法。ErbB3 结合蛋白 1（EBP1）可降低 CRPC 中 AR 及其靶基因的蛋白表达。尽管 EBP1 通过使 AR mRNA 不稳定和抑制蛋白翻译来调节激素敏感性前列腺癌细胞中的 AR，但 EBP1 在 CRPC 中下调 AR 的机制尚不清楚。
使用 Western blot 和细胞裂解物和多核糖体的定量 PCR 分析来评估 AR mRNA、蛋白表达和翻译。
与激素依赖性细胞相反，EBP1 不会改变激素抵抗细胞中 AR mRNA 的稳态水平或 AR mRNA 的稳定性。EBP1 确实会减缓 AR mRNA 的蛋白翻译。EBP1 转染细胞中的 ErbB3/4 配体表皮生长因子样因子进一步减少了 AR 翻译，但在对照细胞中则没有。
这些研究表明，EBP1 下调 AR 水平的一种途径可能在 CRPC 中丢失。
