Ell3 stimulates proliferation, drug resistance, and cancer stem cell properties of breast cancer cells via a MEK/ERK-dependent signaling pathway
Ell3 stimulates proliferation, drug resistance, and cancer stem cell properties of breast cancer cells via a MEK/ERK-dependent signaling pathway
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DOI：
10.1016/j.bbrc.2013.06.114
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发表时间：
2013-08-09
影响因子：
3.1
通讯作者：
Park, Kyung-Soon
中科院分区：
文献类型：
--
作者：
Ahn, Hee-Jin;Kim, Gwangil;Park, Kyung-Soon
E113是一种RNA聚合酶II转录延伸因子，在睾丸中富集。E113的C-末端结构域显示出与E11（11 - 19富含赖氨酸的白血病基因）的C-末端结构域的强烈相似性，E11作为p53的负调节剂并调节细胞增殖和存活。本实验室最近的研究表明，E13通过促进p53降解保护分化细胞免于凋亡而诱导小鼠胚胎干细胞分化。在这项研究中，我们评估了Ell 3在乳腺癌细胞系中的功能。使用过表达E113的MCF-7细胞系来检查细胞增殖和癌症干细胞特性。E113在乳腺癌细胞系中的异位表达诱导增殖和5-FU抗性。此外，E113表达增加了以CD 44（+）或ALDH 1（+）细胞为特征的癌症干细胞群体。在乳腺癌细胞系中，E13表达后，乳腺球形成潜力和迁移能力也增加。通过生物化学和分子生物学分析，我们发现Ell 3部分通过MEK-细胞外信号调节激酶信号通路调节乳腺癌细胞系的增殖、癌症干细胞特性和耐药性。小鼠异种移植实验表明，E113表达促进体内肿瘤发生。这些结果表明，Ell 3可能通过ERK 1/2信号通路调节细胞增殖和癌症干细胞特性，在促进乳腺癌的肿瘤发生中发挥关键作用。(C)2013 Elsevier Inc. All rights reserved.
Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven-nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53 and regulates cell proliferation and survival. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis via the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. MCF-7 cell lines overexpressing Ell3 were used to examine cell proliferation and cancer stem cell properties. Ectopic expression of Ell3 in breast cancer cell lines induces proliferation and 5-FU resistance. In addition, Ell3 expression increases the cancer stem cell population, which is characterized by CD44 (+) or ALDH1 (+) cells. Mammosphere-forming potential and migration ability were also increased upon Ell3 expression in breast cancer cell lines. Through biochemical and molecular biological analyses, we showed that Ell3 regulates proliferation, cancer stem cell properties and drug resistance in breast cancer cell lines partly through the MEK-extracellular signal-regulated kinase signaling pathway. Murine xenograft experiments showed that Ell3 expression promotes tumorigenesis in vivo. These results suggest that Ell3 may play a critical role in promoting oncogenesis in breast cancer by regulating cell proliferation and cancer stem cell properties via the ERK1/2 signaling pathway. (C) 2013 Elsevier Inc. All rights reserved.