钙离子动员对雄激素调节基因表达的影响：AP-1蛋白对雄激素受体介导的反式激活的干扰。
Effects of Ca++ mobilization on expression of androgen-regulated genes: interference with androgen receptor-mediated transactivation by AP-I proteins.
作者信息
Murtha P E, Zhu W, Zhang J, Zhang S, Young C Y
机构信息
Department of Urology, Mayo Clinic/Foundation, Rochester, MN 55909, USA.
出版信息
Prostate. 1997 Dec 1;33(4):264-70. doi: 10.1002/(sici)1097-0045(19971201)33:4<264::aid-pros7>3.0.co;2-h.
BACKGROUND
The adult prostate is maintained through an equilibrium between cell growth and death rates. Androgen deprivation induces an increase in intracellular Ca++, AP-1 gene expression of androgen-inducible genes.
METHODS
Northern blot analysis, band-shift assays, and transient cotransfection assays were used to study the effects of Ca++ mobilizer A23187 on gene expression in human prostate cancer cells.
RESULTS
A23187 repressed androgen-upregulated mRNAs for prostate-specific antigen (PSA) and hKLK2, and rapidly induced mRNA levels for c-fos and c-jun. AP-1 protein-DNA binding activities were elevated after A23187 treatments. Androgen receptor (AR)-mediated induction of chloramphenicol acetyltransferase (CAT) reporter was repressed by AP-1 proteins.
CONCLUSIONS
The repression of AR-mediated induction of PSA and hKLK2 genes by Ca++ mobilizers is due to the interference of AR transactivation activity by AP-1 proteins.
背景
成年前列腺通过细胞生长和死亡率之间的平衡得以维持。雄激素剥夺会导致细胞内钙离子浓度升高，雄激素诱导基因的AP-1基因表达增加。
方法
采用Northern印迹分析、凝胶迁移实验和瞬时共转染实验，研究钙离子载体A23187对人前列腺癌细胞基因表达的影响。
结果
A23187抑制雄激素上调的前列腺特异性抗原（PSA）和hKLK2的mRNA表达，并迅速诱导c-fos和c-jun的mRNA水平升高。A23187处理后，AP-1蛋白与DNA的结合活性增强。AP-1蛋白抑制雄激素受体（AR）介导的氯霉素乙酰转移酶（CAT）报告基因的诱导。
结论
钙离子载体对AR介导的PSA和hKLK2基因诱导的抑制作用是由于AP-1蛋白对AR反式激活活性的干扰。
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