Kikugawa Tadahiko, Kinugasa Yumi, Shiraishi Ken, Nanba Daisuke, Nakashiro Koh-ichi, Tanji Nozomu, Yokoyama Masayoshi, Higashiyama Shigeki
Department of Biochemistry and Molecular Genetics, Ehime University School of Medicine, Shitsukawa, To-on, Ehime, Japan.
Prostate. 2006 Jul 1;66(10):1092-9. doi: 10.1002/pros.20443.
Promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor and negative regulator of the cell cycle, has been characterized as a prostatic androgen-responsive gene. DU145 cells show androgen-independent growth and lack PLZF gene expression.
We analyzed PLZF-regulating genes by DNA microarray using DU145 cells infected with LacZ- or PLZF-carrying adenoviruses.
DNA microarray revealed that Pbx1 is a prominent suppressed gene in PLZF-overexpressing DU145 cells. Androgen receptor (AR)-expressing DU145 cells recovered androgen-dependent PLZF expression and subsequent repression of Pbx1 expression. Immunoprecipitation of Pbx1 in DU145 cells revealed a Pbx1-HoxC8 heterocomplex. siRNAs for Pbx1 and HoxC8 knocked downexpression of each, and this suppressed androgen-independent cell growth. Double knockdown of both Pbx1 and HoxC8 suppressed cell growth much more significantly.
Androgen-independent cell line DU145 cells lack PLZF gene expression, resulting in the upregulation of Pbx1 and HoxC8 expression. The Pbx1-HoxC8 heterocomplex may lead to androgen-independent growth in prostate cancer.
早幼粒细胞白血病锌指（PLZF）蛋白是一种转录抑制因子和细胞周期负调控因子，已被鉴定为前列腺雄激素反应性基因。DU145细胞表现出雄激素非依赖性生长且缺乏PLZF基因表达。
我们使用感染了携带LacZ或PLZF腺病毒的DU145细胞，通过DNA微阵列分析PLZF调控基因。
DNA微阵列显示，Pbx1是PLZF过表达的DU145细胞中一个显著被抑制的基因。表达雄激素受体（AR）的DU145细胞恢复了雄激素依赖性PLZF表达以及随后对Pbx1表达的抑制。对DU145细胞中的Pbx1进行免疫沉淀显示存在Pbx1-HoxC8异源复合物。针对Pbx1和HoxC8的小干扰RNA（siRNA）分别敲低了它们的表达，并且这抑制了雄激素非依赖性细胞生长。同时敲低Pbx1和HoxC8对细胞生长的抑制作用更为显著。
雄激素非依赖性细胞系DU145细胞缺乏PLZF基因表达，导致Pbx1和HoxC8表达上调。Pbx1-HoxC8异源复合物可能导致前列腺癌的雄激素非依赖性生长。
