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

我们假设，由于该基因充当主基因在胚胎中形态发生过程中调节细胞空间信息，因此同源基因基因的失调表达会改变肿瘤细胞的侵入性和转移能力。在这项研究中，将HOXD3基因的哺乳动物表达矢量（I类同源基因之一）或反义HOXD3基因转化为人类肿瘤细胞。为了集体分析HOXD3下游的基因，我们使用大约7,000个元素组成的cDNA微阵列比较了两者之间的基因表达模式。微阵列指示的HOXD3响应基因是为以下5组编码：1）细胞外基质（ECM）成分，2）细胞粘附分子，3）与ECM-核化相关的分子，4）4）细胞骨架系统缔合分子和5）生长因子，相关的分子，Cytokines，Cytokines，Cytokines，Cytokines，Cytokines及其相关分子。我……更值得注意的是，HOXD3反表达导致细胞 - 细胞粘附分子的表达降低，例如Desmoglein，desmoplakin，plakoglobin和e--adherin和E-钙粘着蛋白和E-钙粘着蛋白，并增加与细胞 - 特性型相互作用相关的分子表达MMP-2和UPA。这些基因的表达改变可能会导致在过表达HOXD3的A54 9细胞中的侵袭和转移。为了比较表达反义HOXD3的A375M细胞与意外细胞之间的基因表达模式，我们应用了cDNA微阵列分析。微阵列表明，反义HOXD3的转导增加了Tropomyosin 2和Cdc42相互作用蛋白4的表达，这是细胞骨架系统的组成部分。这些结果表明，HOXD3的失调表达改变了各种相关基因，尤其是那些编码细胞粘附或细胞骨架分子的基因，从而增强了侵袭和转移。较少的