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小鼠乳腺癌生长过程中细胞因子及细胞因子相关基因表达谱分析

Analysis of the expression profiles of cytokines and cytokine-related genes during the progression of breast cancer growth in mice.

作者信息

Jung Mi Young, Kim Seung Hyun, Cho Daeho, Kim Tae Sung

机构信息

Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.

出版信息

Oncol Rep. 2009 Nov;22(5):1141-7. doi: 10.3892/or_00000547.

Abstract

Cytokines are a protein family of regulatory factors derived from tumors and their environmental components that contribute to the growth, invasion and metastasis of breast cancer. However, the way in which tumor progression and cytokines regulate each other is not well understood. In this study, we used an oligoDNA microarray to assess the kinetic expression profile of cytokine genes in tumor tissues and lymph nodes during the progression of tumor growth in mice that had been subcutaneously challenged with breast adenocarcinoma SB5b cells. Our results demonstrated that IL-15, IL-17, IL-18 and IL-18 binding protein (IL-18bp), which are associated with inflammation, were increased in tumor tissues. Conversely, chemokines and their receptors, including CXCR4/CXCL12, CCR7/CCL21, CCL9, CXCL9 and CCL12, were overexpressed in lymph nodes during tumor growth. Furthermore, RT-PCR and Western blot analysis revealed that IL-18, a pro-angiogenic factor in tumors, was up-regulated in tumor tissues. Interestingly, CCR3, IL-1R2, SOCS and IL-20 were up-regulated in tumor tissues, but down-regulated in lymph nodes during tumor growth. This result suggests that the expression of cytokines and cytokine-related genes was differentially regulated, which resulted in a beneficial effect for tumor progression.

摘要

细胞因子是一类蛋白质家族的调节因子,源自肿瘤及其周围环境成分,它们促进乳腺癌的生长、侵袭和转移。然而,肿瘤进展与细胞因子之间相互调节的方式尚未完全明确。在本研究中,我们使用寡核苷酸DNA微阵列来评估在皮下接种乳腺癌SB5b细胞的小鼠肿瘤生长过程中,肿瘤组织和淋巴结中细胞因子基因的动态表达谱。我们的结果表明,与炎症相关的白细胞介素-15(IL-15)、白细胞介素-17(IL-17)、白细胞介素-18(IL-18)和白细胞介素-18结合蛋白(IL-18bp)在肿瘤组织中增加。相反,趋化因子及其受体,包括CXCR4/CXCL12、CCR7/CCL21、CCL9、CXCL9和CCL12,在肿瘤生长过程中在淋巴结中过表达。此外,逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析显示,肿瘤中的促血管生成因子IL-18在肿瘤组织中上调。有趣的是,在肿瘤生长过程中,CCR3、IL-1R2、细胞因子信号转导抑制因子(SOCS)和IL-20在肿瘤组织中上调,但在淋巴结中下调。这一结果表明,细胞因子和细胞因子相关基因的表达受到差异调节,这对肿瘤进展产生了有益影响。

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