PLZF regulates pbxl transcription and Pbx1-HoxC8 complex leads to androgen-independent prostate cancer proliferation
PLZF regulates pbxl transcription and Pbx1-HoxC8 complex leads to androgen-independent prostate cancer proliferation
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DOI：
10.1002/pros.20443
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发表时间：
2006-07-01
期刊：
影响因子：
2.8
通讯作者：
Higashiyama, Shigeki
中科院分区：
文献类型：
--
作者：
Kikugawa, Tadahiko;Kinugasa, Yumi;Higashiyama, Shigeki
背景资料。早幼粒细胞白血病锌指蛋白(PLZF)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基因。方法以携带LacZ或PLZF的腺病毒感染的DU145细胞为研究对象，用DNA微阵列技术分析PLZF基因的表达。结果DNA芯片显示Pbx1基因是PLZF高表达的DU145细胞中显著受抑制的基因。表达雄激素受体(AR)的DU145细胞恢复了雄激素依赖的PLZF表达，并随后抑制了Pbx1的表达。Pbx1在DU145细胞中的免疫沉淀显示Pbx1-HoxC8异源复合体。Pbx1和HoxC8的siRNA下调了它们的表达，从而抑制了雄激素依赖性细胞的生长。结论雄激素非依赖性细胞株DU145细胞缺乏PLZF基因表达，导致Pbx1和HoxC8表达上调。Pbx1-HoxC8异源复合体可能导致前列腺癌雄激素非依赖性生长。
BACKGROUND. 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.METHODS. We analyzed PLZF-regulating genes by DNA microarray using DU145 cells infected with LacZ- or PLZF-carrying adenoviruses.RESULTS. 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 androgenin-dependent cell growth. Double knockdown of both Pbx1 and HoxC8 suppressed cell growth much more significantly.CONCLUSIONS. 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.