Knockdown of lymphoid enhancer factor 1 inhibits colon cancer progression in vitro and in vivo.
Knockdown of lymphoid enhancer factor 1 inhibits colon cancer progression in vitro and in vivo.
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淋巴增强因子 1 的敲低可在体外和体内抑制结肠癌的进展。
DOI：
10.1371/journal.pone.0076596
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nan KJ
中科院分区：
文献类型：
--
作者：
Wang WJ;Yao Y;Jiang LL;Hu TH;Ma JQ;Liao ZJ;Yao JT;Li DF;Wang SH;Nan KJ
淋巴增强因子1(LEF1)在不同的人类肿瘤中的表达经常发生变化。本研究旨在检测LEF1在结肠癌组织中的表达，并探讨下调LEF1在结肠癌细胞系中表达后的表型、基因表达变化及其可能的机制。应用免疫组织化学和定量逆转录聚合酶链式反应技术检测106例结肠癌组织和癌旁正常组织中LEF1的表达。使用LEF1慢病毒敲除LEF1的表达，以评估细胞活力、细胞周期分布、细胞凋亡和基因表达。采用裸鼠移植瘤模型检测LEF1基因敲除的体内效应。结果表明，结肠癌组织中LEF1的表达水平显著高于癌旁正常组织，且与肿瘤的侵袭深度、淋巴结转移、远处转移、TNM分期及总生存期短有关。此外，LEF1基因敲除降低了肿瘤细胞的存活率、侵袭能力、MMP2和MMP9的表达，但诱导了细胞凋亡。裸鼠移植瘤实验表明，LEF1基因敲除可抑制体内肿瘤的形成和生长。此外，在LEF1基因敲除细胞中，Notch通路相关蛋白RBP-jκ和Hes1的表达减少。综上所述，LEF1蛋白在结肠癌组织中过表达，下调LEF1表达抑制了结肠癌的体外和体内生长。这些数据表明，靶向LEF1表达应进一步评估结肠癌的预防和治疗。
Expression of lymphoid enhancer factor 1 (LEF1) is frequently altered in different human cancers. This study aimed to assess LEF1 expression in colon cancer tissues and to explore changed phenotypes, gene expressions, and the possible mechanism after knocked down LEF1 expression in colon cancer cell lines. A total of 106 colon cancer and matched paratumorous normal tissues were used to assess LEF1 expression using immunohistochemistry and qRT-PCR. LEF1 lentivirus was used to knockdown LEF1 expression for the assessment of cell viability, cell cycle distribution, apoptosis, and gene expressions. The nude mouse xenograft assay was performed to detect the effects of LEF1 knockdown in vivo. The data showed that the levels of LEF1 mRNA and protein were significantly increased in human colon cancer tissues compared to the matched paratumorous normal tissues and were associated with infiltration depth, lymph node and distant metastases, advanced TNM (tumor-node-metastasis) stages, and shorter overall survival. Furthermore, LEF1 knockdown reduced tumor cell viability, invasion capacity, MMP2 and MMP-9 expression, but induced apoptosis. Nude mouse xenograft assay showed that LEF1 knockdown suppressed tumor formation and growth in vivo. In addition, the expression of Notch pathway-related proteins RBP-jκ and Hes1 was reduced in LEF1 knockdown cells. Taken together, LEF1 protein was overexpressed in colon cancer tissues and knockdown of LEF1 expression inhibited colon cancer growth in vitro and in vivo. These data suggest that targeting of LEF1 expression should be further evaluated for colon cancer prevention and therapy.
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影响因子：
4.7
作者：
Chen DL;Wang DS;Wu WJ;Zeng ZL;Luo HY;Qiu MZ;Ren C;Zhang DS;Wang ZQ;Wang FH;Li YH;Kang TB;Xu RH
通讯作者：
Xu RH
影响因子：
11.2
作者：
Pannequin, Julie;Bonnans, Caroline;Hollande, Frederic
通讯作者：
Hollande, Frederic
影响因子：
5.3
作者：
Ross, DA;Kadesch, T
通讯作者：
Kadesch, T
影响因子：
14.5
作者：
Bourboulia D;Stetler-Stevenson WG
通讯作者：
Stetler-Stevenson WG
影响因子：
2.1
作者：
Bucan, Vesna;Mandel, Katharina;Hass, Ralf
通讯作者：
Hass, Ralf