Co-expression of the androgen receptor and the transcription factor ZNF652 is related to prostate cancer outcome
Co-expression of the androgen receptor and the transcription factor ZNF652 is related to prostate cancer outcome
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DOI：
10.3892/or_00000731
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发表时间：
2010-04-01
期刊：
影响因子：
4.2
通讯作者：
Holm, Ruth
中科院分区：
文献类型：
--
作者：
Callen, David F.;Ricciardelli, Carmela;Holm, Ruth
ZNF 652是一种DNA结合转录因子，以前曾被认为在前列腺癌中差异表达。本研究探讨ZNF 652和雄激素受体（AR）在前列腺癌中的表达与前列腺特异抗原（PSA）定义的复发之间的关系。在121例前列腺癌患者的前列腺组织中评估ZNF 652和AR免疫反应性，并确定其与疾病结局的相关性。为了评估ZNF 652是否影响AR表达，或反之亦然，在前列腺细胞系LNCaP中，在通过5 α-二氢睾酮诱导AR活性或敲低ZNF 652表达后，测定ZNF 652、AR和PSA的表达水平。三分之二的前列腺肿瘤保持高水平的ZNF 652（71/109例）和50%的肿瘤高水平的AR（57/113）。ZNF 652和AR高表达患者的无复发生存率显著降低（p=0.005），这与术前PSA和精囊受累无关。LNCaP细胞中AR或ZNF 652表达水平的调节与ZNF 652或AR水平的任何相应变化无关。在临床器官定义的前列腺癌中，AR和ZNF 652的高水平表达与复发风险的统计学增加相关。ZNF 652和AR转录因子独立发挥作用，并且提出在AR阳性细胞中持续维持ZNF 652的表达导致有助于复发的基因表达模式。
ZNF652, a DNA binding transcription factor, was previously suggested to be differentially expressed in prostate cancer. This Study investigated if the expressions of ZNF652 and androgen receptor (AR) in prostate cancer are associated with prostate specific antigen (PSA) defined relapse. ZNF652 and AR immunoreactivity were evaluated in prostate tissues from it cohort of 121 patients with prostate cancer and associations with disease outcome determined. To assess if ZNF652 call influence AR expression, or vice versa, levels of expression of ZNF652, AR and PSA were determined in the prostate cell line LNCaP following induction of AR activity by 5 alpha-dihydrotestosterone, or knockdown of ZNF652 expression. Two thirds of prostate tumors retained high levels of ZNF652 (71/109 cases) and 50% of tumors high levels of AR (57/113). There was a significant decrease (p=0.005) in relapse-free Survival of patients with high expression levels of both ZNF652 and AR and this was independent of pre-operative PSA and seminal vesicle involvement. Modulation of either AR or ZNF652 expression levels in LNCaP cells was not associated with any corresponding changes to the levels of either ZNF652 or AR, respectively. High levels of expression of both AR and ZNF652 in clinically organ-defined prostate cancer are associated with a statistically increased risk of relapse. The ZNF652 and AR transcription factors are acting independently and it is proposed that the continued maintenance of expression of ZNF652 in AR positive cells results in a gene expression pattern that contributes to the relapse.