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结蛋白激活Smad和细胞外信号调节激酶1/2通路,促进肾细胞癌增殖。

Nodal activates smad and extracellular signal-regulated kinases 1/2 pathways promoting renal cell carcinoma proliferation.

作者信息

Zhang Zhiwei, Jiang Tao, Li Quanlin, Wang Jianbo, Yang Deyong, Li Xiancheng, Wang Qifei, Song Xishuang

机构信息

Department of Urinary Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China.

出版信息

Mol Med Rep. 2015 Jul;12(1):587-94. doi: 10.3892/mmr.2015.3343. Epub 2015 Feb 12.

Abstract

Expression of the nodal gene is high in a number of tumor cell types and may promote tumor growth. The expression of lefty, an inhibitor of nodal is often reduced in tumor cells. To the best of our knowledge, few studies have investigated the expression of nodal and lefty in renal cell carcinoma (RCC) cells. In the present study, quantitative polymerase chain reaction assays demonstrated that the level of nodal expression in RCC cells was high compared with that of adjacent non-tumor tissue cells, while the opposite pattern was observed for the level of lefty expression. Furthermore, lefty overexpression in RCC cells inhibited the expression of nodal. Nodal overexpression promoted RCC cell proliferation and invasion, and inhibited RCC cell apoptosis. Nodal downregulation and lefty overexpression led to similar observations: The inhibition of RCC cell proliferation and invasion, and the promotion of RCC cell apoptosis. The results of the present study suggested that the expression of nodal promoted RCC growth by activating the smad and extracellular signal-regulated kinases 1/2 pathways. The expression of lefty in RCC cells was lower than that in adjacent non-tumor cells, which may result in the overexpression of nodal, thereby promoting the growth of RCC. The results of the present study may therefore be useful for the development of novel biomarkers for RCC tumor diagnosis, and suggest a potential target gene for the treatment of RCC.

摘要

结节基因在多种肿瘤细胞类型中高表达,可能促进肿瘤生长。结节抑制因子Lefty在肿瘤细胞中的表达常常降低。据我们所知,很少有研究调查过肾细胞癌(RCC)细胞中结节基因和Lefty的表达情况。在本研究中,定量聚合酶链反应分析表明,与相邻的非肿瘤组织细胞相比,RCC细胞中结节基因的表达水平较高,而Lefty的表达水平则呈现相反的模式。此外,RCC细胞中Lefty的过表达抑制了结节基因的表达。结节基因的过表达促进了RCC细胞的增殖和侵袭,并抑制了RCC细胞的凋亡。结节基因下调和Lefty过表达导致了类似的结果:抑制了RCC细胞的增殖和侵袭,并促进了RCC细胞的凋亡。本研究结果表明,结节基因的表达通过激活Smad和细胞外信号调节激酶1/2通路促进了RCC的生长。RCC细胞中Lefty的表达低于相邻的非肿瘤细胞,这可能导致结节基因的过表达,从而促进RCC的生长。因此,本研究结果可能有助于开发用于RCC肿瘤诊断的新型生物标志物,并提示了一个潜在的RCC治疗靶基因。

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