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IL-4/Stat6活性与细胞周期调控和癌转移相关基因的差异性表达

IL-4/Stat6 Activities and Differential Expression of Cell Cycle Regulatory Genes and Metastasis-related Genes in Colon Cancer Cells
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摘要 IL-4诱导的Stat6活化水平在细胞之间差异很大,已发现这种差异与肿瘤细胞增殖、凋亡和侵袭转移力相关。本课题旨在探讨Stat6活化水平与细胞周期调控基因以及癌转移相关基因表达水平之间的相关性并试图解释这种相关性与癌细胞行为的关联。运用半定量RT-PCR法检测细胞周期调控基因CDK4、CDKN2A、CDKN1B、CD-KN1A的方法,以及转移相关基因CD44v6、S100A4、CXCR4、NM23分别在结肠癌细胞系Caco-2(Stat6null表型)、HT-29(Stat6high表型)中的表达水平。显示,结果细胞周期依赖性激酶CDK4,促转移基因CD44v6、S100A4在Stat6high表型的HT-29细胞表达较高的mRNA;而周期抑制基因CDKN2A、CDKN1B、CDKN1A,以及转移抑制基因NM23则在Caco-2(Stat6null表型)细胞表达较高的mRNA,上述差异均有统计学意义(P<0.05)。CXCR4mR-NA表达水平在两株细胞间无统计学差异。由此可知,携带高活化表型Stat6high的癌细胞(HT-29),其细胞周期抑制基因、转移抑制基因表达降低;而细胞周期正向调节基因、促转移基因表达增高。这种基因表达的变化可能对癌细胞的生长、侵袭和转移有利,提示Stat6的活化状态在癌症的发展和预后上可能具有标志物意义。 IL-4-induced Stat6 activities（activation phenotypes） vary among cancer cells,correlating with cancer cells＇ growth,susceptibility to apoptosis and invasiveness/metastasis.This study aims at exploring differential expression of relevant genes related to cell cycle regulation and cell invasiveness/metastasis in human colon cancer cell lines carrying different Stat6 activation phenotypes.Method：Reverse transcriptase PCR（RT-PCR） was used to examine mRNA levels of cell cycle regulator genes CDK4,CDKN2A,CDKN1B and CDKN1A,and invasiveness/metastasis-related genes CD44v6,S100A4,CXCR4 and NM23,in colon cancer cell lines HT-29（Stat6high） and Caco-2（Stat6null）,respectively.Results：Stat6null Caco-2 cells expressed higher mRNA levels of cell cycle inhibitor genes CDKN2A,CDKN1B,CDKN1A and anti-metastatic gene NM23,while Stat6high HT-29 cells exhibited increased expression of cell cycle-dependent kinase CDK4 and pro-metastatic genes CD44v6 and S100A4.Conclusion：Colon cancer cells with Stat6null phenotype correlate with increased expression of cell cycle inhibitory genes and anti-metastatic genes,but decreased expression of cell cycle promoting and pro-metastatic genes.These results suggest a possible role of IL-4/Stat6 activity in regulating genes that regulate colon cancer cells＇ growth/proliferation and invasiveness/metastasis.
作者 马志萍 袁佳 张燕 李本辉 徐双兵 刘晓洪 李锋 张文杰
机构地区 石河子大学医学院病理系/新疆地方与民族高发病教育部重点实验室 湖北省襄樊市中心医院肿瘤科 中山大学肿瘤中心 华中科技大学同济医学院生殖医学中心
出处 《石河子大学学报（自然科学版）》 CAS 2012年第4期466-471,共6页 Journal of Shihezi University(Natural Science)
基金 "十一五"科技支撑计划项目(2009BAI82B02 2009BAI82B03) 国家自然科学基金项目(30871289) 石河子大学绿洲学者基金项目(0263-6000601)
关键词 人类结直肠癌 STAT6 细胞周期 侵袭转移 colon cancer Stat6 cell cycle metastasis
分类号 R735.35 [医药卫生—肿瘤]
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参考文献21

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石河子大学学报（自然科学版）
2012年 第4期

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