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对参与雄激素依赖性前列腺癌转变为雄激素非依赖性过程的多个基因和信号通路进行基因微阵列评估。

Gene microarray assessment of multiple genes and signal pathways involved in androgen-dependent prostate cancer becoming androgen independent.

作者信息

Liu Jun-Bao, Dai Chun-Mei, Su Xiao-Yun, Cao Lu, Qin Rui, Kong Qing-Bo

机构信息

China-Japan Union Hospital of Jilin University, Changchun, Jilin, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(22):9791-5. doi: 10.7314/apjcp.2014.15.22.9791.

DOI:10.7314/apjcp.2014.15.22.9791
PMID:25520106
Abstract

To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-β signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.

摘要

为研究雄激素依赖性前列腺癌(ADPC)转变为去势抵抗性前列腺癌(AIPC)过程中的基因表达变化及可能的信号通路,采用氟他胺联合无雄激素环境诱导建立AIPC的LNCaP细胞模型,并通过基因芯片筛选差异表达基因。然后利用分子注释系统(MAS)分析差异表达基因的生物学过程、分子功能和KEGG通路。通过对12207个表达基因进行比较,获得347个表达基因,其中156个上调,191个下调。对差异表达基因的生物学过程和分子功能进行分析后发现,这些基因在细胞增殖、分化、细胞周期调控、蛋白质代谢与修饰等生物学过程中发挥关键作用,可作为信号分子、酶、肽类激素、细胞因子、细胞骨架蛋白和黏附分子。KEGG分析表明,AIPC转变的相关基因参与谷胱甘肽代谢、细胞周期、P53信号通路、细胞色素P450代谢、Hedgehog信号通路、MAPK信号通路、脂肪细胞因子信号通路、PPAR信号通路、TGF-β信号通路和JAK-STAT信号通路。综上所述,在ADPC转变为AIPC的过程中,发生变化的不仅是一个特定基因或通路,而是多个基因和通路。上述研究结果为AIPC机制的研究及AIPC靶向药物的开发奠定了基础。

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