雌激素促进ER阴性乳腺癌细胞中IL-6的表达
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国家自然科学基金面上项目(81202275);天津市自然科学基金(13JCQNJC11000)


Estrogen enhances expression of interleukin-6 in ER-negative breast cancer cells
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    摘要:

    目的:探讨雌激素作用下G蛋白偶联雌激素受体(G-protein coupled estrogen receptor,GPER)信号通路的活化对ER阴性乳腺癌细胞中白介素 (interleukin,IL)-6表达的影响。方法:药物处理SKBR-3与MDA-MB-453细胞后,实时定量荧光PCR法检测细胞中IL-6 mRNA的变化,ELISA法检测细胞培养上清中IL-6的分泌量,Western blot法检测细胞中p-ERK与p-AKT的蛋白表达水平。结果:17-β雌二醇(E2)和GPER特异性激动剂(G1)显著促进SKBR-3与MDA-MB-453细胞中IL-6的mRNA表达以及细胞上清液中IL-6的分泌量,GPER特异性拮抗剂(G15)可显著抑制以上变化(P < 0.05)。E2及G1药物处理SKBR-3细胞后显著活化细胞内GPER/AKT信号通路以及GPER/ERK信号通路(P < 0.05),上调p-AKT与p-ERK的蛋白表达水平,p-AKT的相对表达量分别为对照组的(4.16 ± 0.65)-(3.21 ± 0.45)倍,p-ERK分别为对照组的(2.87 ± 0.42)-(2.64 ± 0.24)倍,在MDA-MB-453细胞中也可得到类似结果。用MEK特异性抑制剂(U0126)可明显阻断E2及G1所引发的IL-6表达变化(P < 0.05),PI3K特异性抑制剂(Wortmannin)则不能。结论:雌激素可促进ER阴性乳腺癌细胞中IL-6的mRNA表达及细胞上清液中IL-6的分泌量,其机制可能与GPER/ERK信号通路的上调有关,由GPER介导的炎症微环境可能在ER阴性乳腺癌进展中发挥重要作用。

    Abstract:

    Objective:To investigate effects of activated G-protein coupled estrogen receptor(GPER) signaling pathway induced by estrogen on the production of interleukin-6 (IL-6) in ER-negative breast cancer cells. Methods:After treatment of SKBR-3 and MDA-MB-453 cells,the expression of IL-6 mRNA was measured by Real-time qPCR. The secretion of IL-6 in supernatant was detected by ELISA. The protein expression level of p-ERK and p-AKT was determined by Western blot. Results:17-β estradiol (E2) and GPER specific agonist (G1) significantly increased the mRNA expression of IL-6 in SKBR-3 and MDA-MB-453 cells,which could be blocked by GPER specific antagonist (G15). After treatment with E2 and G1,GPER/ERK and GPER/AKT signaling pathways were remarkably activated to promote the protein expression of p-ERK and p-AKT (P < 0.05). The relative protein expressions of p-AKT and p-ERK in the E2 and G1 treatment groups were (4.16 ± 0.65),(3.21 ± 0.45) and (2.87 ± 0.42),(2.64 ± 0.24) times than those of the control group,respectively,and the same results were obtained in MDA-MB-453 cells. Interestingly,these changes induced by E2 and G1 were significantly blocked by the MEK inhibitor U0126 rather than PI3K inhibitor Wortmannin (P < 0.05). Conclusion:Estrogen enhances the expression and secretion of IL-6 in ER(-) breast cancer cells,which may associates with the up-regulation of GPER/ERK signaling pathway,and the inflammatory microenvironment mediated by GPER may play an important role in the development of ER(-) breast cancer.

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王 健,徐 杰,安雪青,吕健东.雌激素促进ER阴性乳腺癌细胞中IL-6的表达[J].南京医科大学学报(自然科学版),2015,(3):309-314

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  • 收稿日期:2014-08-22
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  • 在线发布日期: 2015-03-10
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