RUNX1 and RUNX2 upregulate Galectin-3 expression in human pituitary tumors.
RUNX1 and RUNX2 upregulate Galectin-3 expression in human pituitary tumors.
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DOI：
10.1007/s12020-008-9129-z
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发表时间：
2009-02
期刊：
影响因子：
3.7
通讯作者：
Lloyd, Ricardo V.
中科院分区：
文献类型：
--
作者：
Zhang, He-Yu;Jin, Long;Stilling, Gail A.;Ruebel, Katharina H.;Coonse, Kendra;Tanizaki, Yoshinori;Raz, Avraham;Lloyd, Ricardo V.
半乳糖凝集素-3在人垂体瘤中以细胞类型特异性方式表达，并且可能在垂体瘤的发展中起作用。在这项研究中，我们假设半乳糖凝集素-3在垂体瘤中受到RUNX蛋白的调节。转录因子预测程序揭示了LGALS 3（半乳糖凝集素-3基因）启动子区域中的几个推定结合位点。以人垂体细胞系HP 75为模型，采用染色质免疫沉淀法和电泳迁移率变动法研究LGALS 3和RUNX的相互作用。在LGALS 3启动子区鉴定了两个RUNX 1结合位点和一个RUNX 2结合位点。将LGALS 3启动子进一步克隆到荧光素酶报告基因中，实验表明RUNX 1和RUNX 2均上调LGALS 3。通过siRNA敲低RUNX 1或RUNX 2导致HP 75细胞系中Galectin-3表达的显著下调和细胞增殖的降低。免疫组化显示Galectin-3表达与RUNX 1/RUNX 2水平密切相关。这些结果证明了RUNX 1和RUNX 2蛋白的新结合靶点，并表明半乳糖凝集素-3在人垂体瘤细胞中通过直接结合LGALS 3的启动子区域而受RUNX 1和RUNX 2调节，因此可能有助于垂体瘤进展。
Galectin-3 is expressed in a cell-type specific manner in human pituitary tumors and may have a role in pituitary tumor development. In this study, we hypothesized that Galectin-3 is regulated by RUNX proteins in pituitary tumors. Transcription factor prediction programs revealed several putative binding sites in the LGALS3 (Galectin-3 gene) promoter region. A human pituitary cell line HP75 was used as a model to study LGALS3 and RUNX interactions using Chromatin immunoprecipitation assay and electrophoresis mobility shift assay. Two binding sites for RUNX1 and one binding site for RUNX2 were identified in the LGALS3 promoter region. LGALS3 promoter was further cloned into a luciferase reporter, and the experiments showed that both RUNX1 and RUNX2 upregulated LGALS3. Knock-down of either RUNX1 or RUNX2 by siRNA resulted in a significant downregulation of Galectin-3 expression and decreased cell proliferation in the HP 75 cell line. Immunohistochemistry showed a close correlation between Galectin-3 expression and RUNX1/RUNX2 level in pituitary tumors. These results demonstrate a novel binding target for RUNX1 and RUNX2 proteins and suggest that Galectin-3 is regulated by RUNX1 and RUNX2 in human pituitary tumor cells by direct binding to the promoter region of LGALS3 and thus may contribute to pituitary tumor progression.
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