δEF1 promotes breast cancer cell proliferation through down-regulating p21 expression
δEF1 promotes breast cancer cell proliferation through down-regulating p21 expression
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DOI：
10.1016/j.bbadis.2009.12.002
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发表时间：
2010-02-01
影响因子：
6.2
通讯作者：
Yang, Shuang
中科院分区：
文献类型：
--
作者：
Hu, Fen;Wang, Chuan;Yang, Shuang
尽管锌指同源结构域转录因子 delta EF1 被认为是癌发生过程中增殖和分化十字路口的调节因子，但其在调节细胞周期进展中的潜在作用尚未得到很好的阐明。在我们目前的研究中，我们提供了新的发现，在乳腺癌中，MDA-MB-231 细胞中 delta EF1 的异位表达通过增加细胞周期 S 期的细胞数量来显着促进细胞增殖。相比之下，通过RNA干扰敲低delta EF1表现出相反的效果，突显了delta EF1在促进乳腺癌细胞G1-S转变中的有效作用。此外，我们证明在此过程中 delta EF1 下调 p21，同时上调 CDK2 和 CDK4 的表达。此外，delta EF1 通过招募到 p21 启动子上的 E-2 盒元件来抑制 p21 转录。 MDA-MB-231 细胞中内源 delta EF1 的消耗足以允许 p21 表达的固有释放，从而导致细胞周期停滞。此外，在乳腺癌细胞系和临床肿瘤标本中观察到的 delta EF1 和 p21 表达呈负相关，支持了 delta EF1 通过 p21 调节对细胞增殖的刺激作用。综上所述，这些观察结果表明 delta EF1 通过差异调节细胞周期调节蛋白，在促进乳腺癌细胞增殖方面具有双重作用。 (C) 2009 Elsevier B.V. 保留所有权利。
Although the zinc finger-homeodomain transcription factor delta EF1 is implied as a regulatory factor at the crossroad between proliferation and differentiation in carcinogenesis, its potential effect in the regulation of cell cycle progression has not been well elucidated. In our present study, we provide novel finding that, in breast cancer, the ectopic expression of delta EF1 in MDA-MB-231 cells significantly promoted cell proliferation by increasing the cell number in S phase of the cell cycle. In contrast, delta EF1 knockdown by RNA interference exhibited an opposite effect, highlighting a potent role of delta EF1 to promote G1-S transition of breast cancer cells. Moreover, we demonstrated that delta EF1 down-regulated p21 and concurrently up-regulated the expressions of CDK2 and CDK4 during this process. Further, delta EF1 inhibited p21 transcription by recruiting to the E-2 box element on the p21 promoter. Depletion of endogenous delta EF1 in MDA-MB-231 cells was sufficient to allow an inherent release of p21 expression, thus resulting in the cell cycle arrest. In addition, the stimulatory effect of delta EF1 on cell proliferation through p21 regulation was supported by an inverse correlation of delta EF1 and p21 expressions observed in both breast cancer cell lines and clinical tumor specimens. Taken together, these observations suggest a dual effect of delta EF1 in promoting breast cancer cell proliferation, by differentially regulating the cell cycle regulatory proteins. (C) 2009 Elsevier B.V. All rights reserved.