Characterization of the prostate cancer susceptibility gene KLF6 in human and mouse prostate cancers
Characterization of the prostate cancer susceptibility gene KLF6 in human and mouse prostate cancers
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DOI：
10.1002/pros.22554
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发表时间：
2013-01-01
期刊：
影响因子：
2.8
通讯作者：
Bianco-Miotto, Tina
中科院分区：
文献类型：
--
作者：
Chiam, Karen;Ryan, Natalie K.;Bianco-Miotto, Tina
Kruppel样因子（KLF）6是前列腺癌的候选抑癌基因，但其表达缺失的机制尚不清楚。我们的特点是KLF 6的表达和DNA甲基化状态在前列腺肿瘤的发生在人类和小鼠。方法KLF 6的表达进行了评估，在匹配的人类非恶性（NM）和肿瘤前列腺组织（n？22)通过定量实时PCR（qPCR）和在三个独立的人前列腺癌队列中进行生物信息学分析。在5-氮杂-2 '-脱氧胞苷处理后的人前列腺LNCaP癌细胞中进行KLF 6表达的QPCR和甲基化敏感性PCR（MSP）。采用免疫组化法和MSP法分别检测KLF 6蛋白和DNA启动子甲基化水平。0.0015）。总的来说，与原发性前列腺癌相比，转移性前列腺癌中KLF 6的表达降低，原发性肿瘤中KLF 6的表达降低与复发时间缩短相关（P = 0.001）。0.0028）。用去甲基化剂5-氮杂-2 '-脱氧胞苷处理导致KLF 6表达上调（2倍; P = 0.001）。0.002）和LNCaP细胞中KLF 6启动子的DNA甲基化降低。Klf 6蛋白水平在前列腺癌TRAMP模型中随着进展而显著降低（P？
BACKGROUND Kruppel-like factor (KLF) 6 is a candidate tumor suppressor gene in prostate cancer, but the mechanisms contributing to its loss of expression are poorly understood. We characterized KLF6 expression and DNA methylation status during prostate tumorigenesis in humans and mice.METHODS KLF6 expression was assessed in matched human non-malignant (NM) and tumor prostate tissues (n?=?22) by quantitative real-time PCR (qPCR) and in three independent human prostate cancer cohorts bioinformatically. QPCR for KLF6 expression and methylation-sensitive PCR (MSP) were performed in human prostate LNCaP cancer cells after 5-aza-2'-deoxycytidine treatment. Klf6 protein levels and DNA promoter methylation were assessed in TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) tumors by immunohistochemistry and MSP, respectively.RESULTS KLF6 splice variants expression was increased (P?=?0.0015) in human prostate tumors compared to NM tissues. Overall, KLF6 was decreased in metastatic compared to primary prostate cancers and reduced expression in primary tumors was associated with a shorter time to relapse (P?=?0.0028). Treatment with the demethylating agent 5-aza-2'-deoxycytidine resulted in up-regulation of KLF6 expression (two-fold; P?=?0.002) and a decrease in DNA methylation of the KLF6 promoter in LNCaP cells. Klf6 protein levels significantly decreased with progression in the TRAMP model of prostate cancer (P?