The erythropoietin/erythropoietin receptor signaling pathway promotes growth and invasion abilities in human renal carcinoma cells.
The erythropoietin/erythropoietin receptor signaling pathway promotes growth and invasion abilities in human renal carcinoma cells.
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促红细胞生成素/促红细胞生成素受体信号通路促进人肾癌细胞的生长和侵袭能力
DOI：
10.1371/journal.pone.0045122
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gong K
中科院分区：
文献类型：
--
作者：
Wu P;Zhang N;Wang X;Zhang C;Li T;Ning X;Gong K
促红细胞生成素（Epo）和促红细胞生成素受体（EpoR）在多种非造血系统肿瘤（包括遗传性和散发性肾细胞癌（RCC））中共表达，但Epo/EpoR在肿瘤进展中的自分泌和旁分泌机制尚未明确。本研究利用RNA干扰技术下调EpoR表达，探讨Epo/EpoR通路在人肾细胞癌细胞中的作用。Epo和EpoR在原代肾癌细胞和6种人肾细胞癌细胞系中共表达。原代肾癌细胞786-0和Caki-1的EpoR信号通路存在结构性磷酸化，重组人Epo（rhEpo）刺激对EpoR信号通路的进一步磷酸化、细胞增殖和侵袭力无明显影响。慢病毒介导的siRNA下调786-0细胞中EpoR的表达，抑制细胞的生长和侵袭，促进细胞凋亡。此外，rhEpo刺激轻微拮抗舒尼替尼对786-0细胞的抗肿瘤作用。舒尼替尼可诱导EpoR表达下调的786-0细胞中更多的凋亡细胞。我们的研究结果表明，Epo/EpoR通路参与肾癌细胞的生长，侵袭，存活和对多激酶抑制剂舒尼替尼的敏感性。
Co-expression of erythropoietin (Epo) and erythropoietin receptor (EpoR) has been found in various non-hematopoietic cancers including hereditary and sporadic renal cell carcinomas (RCC), but the Epo/EpoR autocrine and paracrine mechanisms in tumor progression have not yet been identified. In this study, we used RNA interference method to down-regulate EpoR to investigate the function of Epo/EpoR pathway in human RCC cells. Epo and EpoR co-expressed in primary renal cancer cells and 6 human RCC cell lines. EpoR signaling was constitutionally phosphorylated in primary renal cancer cells, 786-0 and Caki-1 cells, and recombinant human Epo (rhEpo) stimulation had no significant effects on further phosphorylation of EpoR pathway, proliferation, and invasiveness of the cells. Down-regulation of EpoR expression in 786-0 cells by lentivirus-introduced siRNA resulted in inhibition of growth and invasiveness in vitro and in vivo, and promotion of cell apoptosis. In addition, rhEpo stimulation slightly antagonized the anti-tumor effect of Sunitinib on 786-0 cells. Sunitinib could induce more apoptotic cells in 786-0 cells with knockdown EpoR expression. Our results suggested that Epo/EpoR pathway was involved in cell growth, invasion, survival, and sensitivity to the multi-kinases inhibitor Sunitinib in RCC cells.
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影响因子：
3.6
作者：
Gong, Kan;Zhang, Ning;Na, Yanqun
通讯作者：
Na, Yanqun
影响因子：
19.6
作者：
Levy, AP;Levy, NS;Goldberg, MA
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Goldberg, MA
影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
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4.8
作者：
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影响因子：
6.4
作者：
Wiesener, Michael S.;Muenchenhagen, Philine;Eckardt, Kai-Uwe
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Eckardt, Kai-Uwe