ELF5 isoform expression is tissue-specific and significantly altered in cancer.
ELF5 isoform expression is tissue-specific and significantly altered in cancer.
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ELF5同工型表达是组织特异性的，并且在癌症中显着改变。
DOI：
10.1186/s13058-015-0666-0
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发表时间：
2016-01-07
期刊：
影响因子：
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通讯作者：
Ormandy CJ
中科院分区：
文献类型：
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作者：
Piggin CL;Roden DL;Gallego-Ortega D;Lee HJ;Oakes SR;Ormandy CJ
E74 样因子 5 (ELF5) 是 E26 转化序列 (ETS) 转录因子家族的上皮特异性成员，也是胎盘、肺支气管和乳腺产奶肺泡中细胞命运的关键调节因子。 ELF5还在恶性肿瘤中发挥着关键作用，特别是在基底样乳腺癌和内分泌抵抗型乳腺癌中。几乎所有基因都会经历选择性转录或剪接，这增加了蛋白质结构和功能的多样性。尽管ELF5具有多种亚型，但在之前的ELF5功能研究中并未考虑到这一点。对来自癌症基因组图谱的 6757 个样本的 RNA 测序数据进行了分析，以表征多种正常组织和癌症中 ELF5 亚型的表达。在乳腺癌细胞系中对 ELF5 同工型进行了广泛的体外分析，包括 116 基因定量聚合酶链式反应组。由于使用了替代启动子，ELF5 亚型表达被发现具有组织特异性，但在多种癌症类型中发生了改变。正常乳腺表达一种主要亚型，而乳腺癌中存在亚型特异性的表达变化。其他 ETS 因子的表达在乳腺癌中也显着改变，基底样亚型表现出独特的 ETS 表达谱。全长亚型 1 和 2 以及亚型 3（缺少 Pointed 结构域）的体外诱导表达具有相似的表型和转录效应。替代启动子的使用赋予不同的调节反应，是控制 ELF5 作用的主要机制，而不是异构体的差异转录活性。对异构体水平表达和功能的理解是实现 ELF5 等转录因子作为癌症预后标志物或治疗靶点的潜力的重要第一步。本文的在线版本 (doi:10.1186/s13058-015-0666-0) 包含补充材料，可供授权用户使用。
E74-like factor 5 (ELF5) is an epithelial-specific member of the E26 transforming sequence (ETS) transcription factor family and a critical regulator of cell fate in the placenta, pulmonary bronchi, and milk-producing alveoli of the mammary gland. ELF5 also plays key roles in malignancy, particularly in basal-like and endocrine-resistant forms of breast cancer. Almost all genes undergo alternative transcription or splicing, which increases the diversity of protein structure and function. Although ELF5 has multiple isoforms, this has not been considered in previous studies of ELF5 function. RNA-sequencing data for 6757 samples from The Cancer Genome Atlas were analyzed to characterize ELF5 isoform expression in multiple normal tissues and cancers. Extensive in vitro analysis of ELF5 isoforms, including a 116-gene quantitative polymerase chain reaction panel, was performed in breast cancer cell lines. ELF5 isoform expression was found to be tissue-specific due to alternative promoter use but altered in multiple cancer types. The normal breast expressed one main isoform, while in breast cancer there were subtype-specific alterations in expression. Expression of other ETS factors was also significantly altered in breast cancer, with the basal-like subtype demonstrating a distinct ETS expression profile. In vitro inducible expression of the full-length isoforms 1 and 2, as well as isoform 3 (lacking the Pointed domain) had similar phenotypic and transcriptional effects. Alternative promoter use, conferring differential regulatory responses, is the main mechanism governing ELF5 action rather than differential transcriptional activity of the isoforms. This understanding of expression and function at the isoform level is a vital first step in realizing the potential of transcription factors such as ELF5 as prognostic markers or therapeutic targets in cancer. The online version of this article (doi:10.1186/s13058-015-0666-0) contains supplementary material, which is available to authorized users.