Characterization of Histone Deacetylase Expression Within In Vitro and In Vivo Bladder Cancer Model Systems
Characterization of Histone Deacetylase Expression Within In Vitro and In Vivo Bladder Cancer Model Systems
复制标题
DOI：
10.3390/ijms20102599
复制
发表时间：
2019-05-02
影响因子：
5.6
通讯作者：
DeGraff, David J.
中科院分区：
文献类型：
--
作者：
Buckwalter, Jenna M.;Chan, Wilson;DeGraff, David J.
表观遗传畸变在膀胱癌（BC）中很突出，并有助于疾病的发病机制。我们在体外和体内BC模型系统中表征了组蛋白去乙酰化酶（HDAC）（一个去乙酰化酶家族）的表达，并分析了来自癌症基因组图谱（TCGA）的表达数据。使用定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹分析来确定10个人BC细胞系中I类和II类HDAC的表达状态，同时使用qRT-PCR来确定24个人肿瘤标本中HDAC的表达。TCGA组群由408个肌肉浸润性BC（MIBC）临床样品组成，并且对该数据集的分析将HDAC 4和HDAC-9的表达鉴定为与基底鳞状疾病相关。这些发现与qRT-PCR结果一致，其鉴定了基底BC细胞系（p < 0.05; Kruskal-Wallis检验）和具有浸润性膀胱癌的临床样本（无统计学显著性）中HDAC 4、HDAC-7和HDAC-9的表达增加。我们还在常用的BC小鼠模型中观察到Hdac 4、-7和-9的表达增加。在这里，我们确定了用于HDAC研究的合适的临床前模型系统，并显示了在基础BC细胞系和侵袭性临床标本中IIa类HDAC，特别是HDAC 4和HDAC 9的表达增加。这些结果表明，这类HDAC可能最适合用于基础BC患者的靶向抑制。
Epigenetic aberrations are prominent in bladder cancer (BC) and contribute to disease pathogenesis. We characterized histone deacetylase (HDAC) expression, a family of deacetylation enzymes, in both in vitro and in vivo BC model systems and analyzed expression data from The Cancer Genome Atlas (TCGA). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis was used to determine the expression status of Class I and II HDACs in ten human BC cell lines, while qRT-PCR was used to determine HDAC expression in 24 human tumor specimens. The TCGA cohort consists of 408 muscle invasive BC (MIBC) clinical samples and analysis of this data set identified expression of HDAC4 and -9 as being associated with basal-squamous disease. These findings agree with qRT-PCR results identifying increased expression of HDAC4, -7, and -9 in basal BC cell lines (p < 0.05; Kruskal-Wallis test) and in clinical specimens with invasive bladder cancer (not statistically significant). We also observed increased expression in Hdac4, -7, and -9 in commonly used BC mouse models. Here, we identify suitable preclinical model systems for the study of HDACs, and show increased expression of Class IIa HDACs, specifically HDAC4 and HDAC9, in basal BC cell lines and in invasive clinical specimens. These results suggest this class of HDACs may be best suited for targeted inhibition in patients with basal BC.