MAPKs通路在胰岛素促人乳腺癌细胞系增殖中的机制研究
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江苏省教育厅基金项目(05KJD310130)


Role of MAPKs signal transduction system in the proliferation of mammary carcinoma cell line MCF-7 induced by insulin
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    摘要:

    目的:探讨丝裂原活化蛋白激酶(mitogen activated protein kinases,MAPKs)信号转导通路在胰岛素促人乳腺癌细胞MCF-7增殖中的作用机制-方法:通过MTT比色法观察不同浓度(0-25-50-100-200 nmol/L)胰岛素促MCF-7细胞的增殖效应,及用JNK-ERK1/2通路特异性抑制剂(SP600125-PD98059)阻断MAPKs信号通路对胰岛素促MCF-7细胞增殖效应的影响; Western blot检测胰岛素干预对磷酸化JNK-磷酸化ERK1/2蛋白表达水平的影响以及JNK-ERK1/2-JAK2特异性抑制剂对上述蛋白表达的影响-结果:各浓度胰岛素均能不同程度促进人乳腺癌细胞MCF-7增殖,25 nmol/L胰岛素的促增殖效应最强(P < 0.01);分别用SP600125-PD98059-AG490阻断JNK-ERK1/2-JAK/STAT信号通路均可不同程度抑制胰岛素促MCF-7细胞的增殖效应;胰岛素可诱导MAPKs信号通路中靶蛋白的磷酸化激活,Western blot结果显示,100 nmol/L胰岛素作用于MCF-7细胞5 min后即可磷酸化激活JNK途径,且该活化状态可持续1hr,而ERK1/2蛋白在胰岛素作用30 min后才被磷酸化激活;10 μmol/L PD98059(ERK通路抑制剂)可显著抑制200 nmol/L 胰岛素作用30 min对ERK1/2的磷酸化激活,而20 μmol/L SP600125(JNK通路抑制剂)以及20 μmol/L AG490(JAK/STAT通路抑制剂)对ERK1/2磷酸化激活的抑制作用则不明显-结论:胰岛素可促进人乳腺癌细胞MCF-7增殖,该增殖效应可能与其激活MAPKs信号通路及下游其他信号转导有关,上述通路的激活可能促进乳腺癌的发生发展-

    Abstract:

    Objective: To explore the role of MAPKs signal transduction system in the proliferation of human mammary carcinoma cell line MCF-7 induced by insulin. Methods:Human mammary carcinoma cell line MCF-7 was treated with different concentrations of insulin(0 nmol/L,25 nmol/L,50 nmol/L,100 nmol/L,200 nmol/L). MTT assay was used to explore the proliferation of MCF-7 cells with or without MAPKs signals blocked by their specific inhibitors which were SP600125, the inhibitor of the phosphorylation of JNK,and PD98059, the inhibitor of the phosphorylation of ERK1/2. The expressions of phospho-JNK and phospho-ERK1/2 at different time treated with insulin were detected by Western blot, and changes of those proteins expressions were observed when MAPKs signals blocker was added. Results:Insulin can promote the proliferation of MCF-7 cells in a concentration-dependent manner. Western blot result implicated that 100 nmol/L insulin induced the activation of JNK and ERK. The phosphrylation of JNK was detected beginning at 5 minutes after insulin treated and sustaining for an hour, while the activation of ERK was at the 30th minute after insulin treated and later than that of JNK. Then we reevaluated the proliferation effect promoted by insulin after MAPKs signaling pathway blocked by their inhibitors. The results showed that after the activities of JNK, ERK and JAK/STAT inhibited, the proliferation effect of insulin was also attenuated. Otherwise,Western blot result showed that, while blocking the MAPKs signaling pathway,10 μmol/L PD98059 could inhibit the activation of ERK1/2 induced by 200 nmol/L insulin,while 20 μmol/L SP600125 and 20 μmol/L AG490 couldn’t inhibit the activation of ERK1/2 obviously. Conclusion: Insulin can stimulate the proliferation of MCF-7 cells in vitro, and MAPKs signal transduction system involves in the proliferation of MCF-7 cells, which could mediate and promote mammary carcinoma development.

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钱晓娟,袁小青,马向华,沈 捷,丁 娇. MAPKs通路在胰岛素促人乳腺癌细胞系增殖中的机制研究[J].南京医科大学学报(自然科学版),2011,(5):684-688

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  • 收稿日期:2010-12-22
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