外源性IK1表达对垂体生长激素基因表达的调节  

Regulation of pituitary growth hormone gene expression by exogenous Ik1 expression

作　　者：于顺江[1,2] 陈力[1,2] 王京[1,3] 

机构地区：[1]北京世纪坛医院 [2]北京大学第九临床学院肿瘤放疗科,北京100038 [3]北京大学第九临床学院病理科,北京100038

出　　处：《中华肿瘤防治杂志》2010年第20期1613-1616,共4页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:研究Ikaros在调节垂体生长激素(GH)基因表达的作用。方法:应用系列的细胞与分子生物学技术如细胞培养、稳定转染、免疫组化、Northern Blot(N.B)、蛋白质印记、染色质免疫共沉淀等方法分析Ik1及其同工蛋白Ik-6在垂体GH基因表达调节中的作用。结果:野生型Ikaros(Ik1)在垂体GH4细胞中抑制了GH基因mRNA和蛋白的表达水平。Ikaros不直接与GH基因启动子结合,但能抑制TSA引起的GH基因启动子的组蛋白乙酰化作用。Ik1能够选择性地抑制GH启动区的染色质组蛋白-3的乙酰化作用,因而阻碍了Pit1与GH启动子DNA的结合。结论:Ikaros在垂体激素基因表达过程中抑制了GH基因的表达(分泌),这一研究为功能性垂体腺瘤GH过度分泌的分子靶向治疗提供了新的参考。OBJECTIVE：To study the effect of the transcription factor Ikaros on the regulations of GH gene expression in pituitary.METHODS：Various cell and molecular biological techniques including cell culture,transfection,immunohistochemistry （IHC）,Northern Blot,Western blot analysis,ChIP-PCR assay,etc.were utilized to examine the expression of Ikaros in GH4 cells,and the impact of the expressed Ikaros and its isoform Ik-6 on expression of the GH gene were observed.RESULTS：Ikaros （Ik1） expressed and regulated the GH gene in GH4 cells.Northern and Western blotting analysis showed Ikaros inhibited GH mRNA and protein expressions.Ikaros did not bind directly to the proximal GH promoter but abrogated the effect of the histone deacetylation inhibitor Trichostatin-A.Ikaros selectively deacetylated histone-3 residues on the transfected and endogenous GH promoter.CONCLUSION：These data show the evidence for Ikaros-mediated histone deacetylation as well as chromatin remodeling in the selective inhibition of pituitary GH gene expression,and provide clinically an insight for molecular targeted treatments against functional hormone over-secreted pituitary adenomas.

关 键 词：IKAROS 基因表达 垂体腺瘤 生长激素 

分 类 号：R736.4[医药卫生—肿瘤]