Pascal Laura E, Masoodi Khalid Z, Liu June, Qiu Xiaonan, Song Qiong, Wang Yujuan, Zang Yachen, Yang Tiejun, Wang Yao, Rigatti Lora H, Chandran Uma, Colli Leandro M, Vencio Ricardo Z N, Lu Yi, Zhang Jian, Wang Zhou
Department of UrologyUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Transcriptomics LabDivision of Plant Biotechnology, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Srinagar, Jammu and Kashmir, India.
J Endocrinol. 2017 Nov;235(2):123-136. doi: 10.1530/JOE-17-0112.
Elongation factor, RNA polymerase II, 2 (ELL2) is an RNA Pol II elongation factor with functional properties similar to ELL that can interact with the prostate tumor suppressor EAF2. In the prostate, is an androgen response gene that is upregulated in benign prostatic hyperplasia (BPH). We recently showed that ELL2 loss could enhance prostate cancer cell proliferation and migration, and that gene expression was downregulated in high Gleason score prostate cancer specimens. Here, prostate-specific deletion of ELL2 in a mouse model revealed a potential role for ELL2 as a prostate tumor suppressor -knockout mice exhibited prostatic defects including increased epithelial proliferation, vascularity and PIN lesions similar to the previously determined prostate phenotype in -knockout mice. Microarray analysis of prostates from -knockout and wild-type mice on a C57BL/6J background at age 3 months and qPCR validation at 17 months of age revealed a number of differentially expressed genes associated with proliferation, cellular motility and epithelial and neural differentiation. OncoPrint analysis identified combined downregulation or deletion in prostate adenocarcinoma cases from the Cancer Genome Atlas (TCGA) data portal. These results suggest that ELL2 and its pathway genes likely play an important role in the development and progression of prostate cancer.
延伸因子，RNA聚合酶II，2（ELL2）是一种RNA聚合酶II延伸因子，其功能特性与ELL相似，可与前列腺肿瘤抑制因子EAF2相互作用。在前列腺中，它是一种雄激素反应基因，在良性前列腺增生（BPH）中上调。我们最近发现，ELL2缺失可增强前列腺癌细胞的增殖和迁移，并且在高Gleason评分的前列腺癌标本中该基因表达下调。在这里，在小鼠模型中前列腺特异性缺失ELL2揭示了ELL2作为前列腺肿瘤抑制因子的潜在作用——敲除小鼠表现出前列腺缺陷，包括上皮增殖增加、血管生成和前列腺上皮内瘤变，类似于之前在敲除小鼠中确定的前列腺表型。对3个月大的C57BL/6J背景的敲除小鼠和野生型小鼠的前列腺进行微阵列分析，并在17个月大时进行qPCR验证，发现了许多与增殖、细胞运动以及上皮和神经分化相关的差异表达基因。OncoPrint分析确定了来自癌症基因组图谱（TCGA）数据门户的前列腺腺癌病例中的联合下调或缺失情况。这些结果表明，ELL2及其通路基因可能在前列腺癌的发生和发展中起重要作用。
