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Homeobox gene that regulated expressions of metastasis-related genes

调节转移相关基因表达的同源盒基因

基本信息

批准号：
11470053
负责人：
HAMADA Jun-ichi
金额：
$ 4.8万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470053/
关键词：
Homeobox gene Invasion and metastasis integrin HOXD3 cDNA microarray lung cancer cell Cadherin malignant melanoma MMP-2 uPA プラコグロビン CD44

项目摘要

We hypothesized that deregualted expression of homeobox genes would modify the invasive and metastatic ability of tumor cells since the genes act as master genes regulating cellular spatial information during morphogenesis in embryo. In this study, mammalian expression vectors for HOXD3 gene (one of class I homeobox genes) or antisense HOXD3 gene were transduced into human tumor cells.I.mRNA was extracted from HOXD3-overexpressing human lung cancer A549 cells and unexpressing control A549 cells. To collectively analyze the genes in the downstream of HOXD3, we compared gene expression patterns between the two by using cDNA microarray consisting of approximately 7,000 elements. HOXD3-responsive genes indicated by the microarray were to code the following 5 groups : 1) extracellular matrix (ECM) components, 2) cell adhesion molecules, 3) molecules associated with ECM-degradation, 4) cytoskeletal system-associated molecules and 5) growth factors, cytokines and their related molecules. It i … More s noteworthy that HOXD3-overexpression resulted in reduced expression of cell-cell adhesion molecules such as desmoglein, desmoplakin, plakoglobin and E-cadherin and increased expression of molecules associated with cell-extracellular matrix interaction such as integrin α4, β3, CD44, thrombospondin, plasminogen activator inhibitor, MMP-2 and uPA.The altered expression of these genes may result in enhancement of invasion and metastasis in HOXD3-overexpressing A54 9 cells.II.The transduction of HOXD3 antisense into human melanoma A375M cells resulted in reduced cell motility and invasion. To compare gene expression patterns between A375M cells expressing antisense HOXD3 and unexpressing cells, we applied cDNA microarray analysis. The microarray revealed that the transduction of antisense HOXD3 increased expressions of tropomyosin 2 and cdc42-interacting protein 4 which were components of cytoskeletal system.These results indicated that deregulated expression of HOXD3 altered a variety of metastasisrelated genes, especially those coding cell adhesion or cytoskeletal molecules, resulting in enhancing invasion and metastasis. Less

我们推测同源异型盒基因的异常表达可能会改变肿瘤细胞的侵袭和转移能力，因为这些基因在胚胎形态发生过程中充当调节细胞空间信息的主基因。本研究将Ⅰ类同源异型盒基因之一HOXD 3基因及其反义基因的真核表达载体分别导入人肺癌细胞A549和正常人肺癌细胞A549中，提取HOXD 3基因的mRNA。为了共同分析HOXD 3下游的基因，我们使用由约7，000个元件组成的cDNA微阵列比较了两者之间的基因表达模式。由微阵列指示的HOXD 3响应基因编码以下5组：1）细胞外基质（ECM）组分，2）细胞粘附分子，3）与ECM降解相关的分子，4）细胞骨架系统相关分子和5）生长因子、细胞因子及其相关分子。它我 ...更多信息值得注意的是，HOXD 3过表达导致细胞-细胞粘附分子如桥粒芯糖蛋白、桥粒斑蛋白、斑珠蛋白和E-钙粘蛋白的表达减少，以及与细胞-细胞外基质相互作用相关的分子如整合素α4、β3、CD 44、血小板反应蛋白、纤溶酶原激活物抑制剂、MMP-2和uPA表达的改变可能导致HOXD 3 - 1细胞侵袭和转移的增强。II. HOXD 3反义核酸转导入人黑色素瘤A375 M细胞导致细胞运动性和侵袭性降低。为了比较表达反义HOXD 3的A375 M细胞和未表达细胞之间的基因表达模式，我们应用cDNA微阵列分析。基因芯片结果显示，反义HOXD 3基因转染后，细胞骨架系统中的原肌球蛋白2（tropomyosin 2）和cdc 42相互作用蛋白4（cdc 42 interacting protein 4）的表达增加，表明HOXD 3基因表达异常改变了多种转移相关基因，尤其是编码细胞粘附和细胞骨架分子的基因，从而增强了肿瘤的侵袭和转移。少