EBP1 inhibits translation of androgen receptor mRNA in castration resistant prostate cancer cells.
EBP1 inhibits translation of androgen receptor mRNA in castration resistant prostate cancer cells.
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发表时间：
2011-10
影响因子：
2
通讯作者：
Hua Zhou;Yuexing Zhang;A. Hamburger
中科院分区：
文献类型：
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作者：
Hua Zhou;Yuexing Zhang;A. Hamburger
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。ErbB 3结合蛋白1（EBP 1）可降低CRPC中AR及其靶基因的蛋白表达。尽管EBP 1通过使AR mRNA不稳定和抑制蛋白质翻译来调节CRPC敏感性前列腺癌细胞中的AR，但EBP 1下调CRPC中AR的机制尚不清楚。材料与方法采用Western blot和定量PCR分析细胞裂解物和多聚体，以评估AR mRNA，蛋白质表达和翻译。结果与激素依赖性细胞相反，EBP 1不改变激素抵抗细胞中AR mRNA的稳态水平或AR mRNA的稳定性。EBP 1使AR mRNA的蛋白翻译减慢。ErbB 3/4配体heregulin进一步减少了EBP 1转染细胞中的AR翻译，但在对照细胞中没有。结论在CRPC中，EBP 1下调AR水平的途径之一可能缺失。
BACKGROUND 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. MATERIALS AND METHODS Western blot and quantitative PCR analysis of cell lysates and polysomes were used to assess AR mRNA, protein expression and translation. RESULTS 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. CONCLUSION These studies suggest that one pathway of EBP1 down-regulation of AR levels may be lost in CRPC.