Sterol regulatory element-binding protein 1 is required for ovarian tumor growth
Sterol regulatory element-binding protein 1 is required for ovarian tumor growth
复制标题
卵巢肿瘤生长需要甾醇调节元件结合蛋白1
DOI：
10.3892/or.2013.2575
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发表时间：
2013-09-01
期刊：
影响因子：
4.2
通讯作者：
Jiang, Jie
中科院分区：
文献类型：
--
作者：
Nie, Long-Yun;Lu, Qing-Tao;Jiang, Jie
脂肪生成信号的重编程是肿瘤细胞病理学的最显著改变之一。与对脂质的大量需求一致，肿瘤细胞表达高水平的脂肪生成酶，其中大部分是固醇调节元件结合蛋白1（SREBP 1）的转录靶点。然而，SREBP1在卵巢癌中的表达水平和功能在很大程度上是未知的。我们的研究旨在评估SREBP1在卵巢癌中的致癌潜力。在这项研究中，我们通过免疫组织化学染色发现，SREBP 1蛋白在人类卵巢癌中的表达显著高于良性和交界性卵巢肿瘤。在卵巢癌细胞中通过小发夹RNA（shRNA）敲低SREBP1抑制细胞生长、迁移和侵袭，并增强细胞凋亡，而对细胞周期分布没有显著影响。在异种移植的SCID小鼠模型中，SREBP1沉默抑制体内肿瘤生长，并在蛋白质和mRNA水平上降低SREBP1下游脂肪生成基因的表达。总之，这项研究的结果证明了SREBP 1在卵巢癌生长中的关键作用，这使SREBP 1成为抗肿瘤治疗的新靶点。
Re-programming of lipogenic signaling is one of the most significant alterations of tumor cell pathology. Consistent with a large demand for lipids, tumor cells express high levels of lipogenic enzymes, most of which are transcriptional targets of sterol regulatory element-binding protein 1 (SREBP1). However, the expression levels and the function of SREBP1 in ovarian cancer are largely unknown. Our study aimed to assess the oncogenic potential of SREBP1 in ovarian cancer. In this study, we showed that the SREBP1 protein expression was significantly higher in human ovarian cancer compared to benign and borderline ovarian tumors by immunohistochemical staining. Knockdown of SREBP1 by small hairpin RNA (shRNA) in ovarian cancer cells retarded cell growth, migration and invasion and enhanced cell apoptosis without significant effects on cell cycle distribution. In a xenograft SCID mouse model, SREBP1 silencing inhibited tumor growth in vivo and reduced the expression of SREBP1 downstream lipogenic genes at both the protein and mRNA levels. Taken together, the results from this study demonstrate a crucial role of SREBP1 in ovarian cancer growth, which establish SREBP1 as a novel therapeutic target for antitumor therapy.