The analysis of OS-4 like gene and homeo protein like gene as a putative choriocarcinoma suppressor gene.

OS-4样基因和同源蛋白样基因作为假定的绒毛膜癌抑制基因的分析。

• 批准号: 13671728
• 负责人: MATSUDA Takao
• 金额: $ 2.43万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671728/
• 关键词: Choriocarcinoma; HTF12; KRAB domain; Zn finger domain; Deterioration; NECC1; homeobox; HOP; KRAV; Kruppel; Zinc finger; choriocarcinoma; homeo domain; hPL

For the isolation of the putative choriocarcinoma suppressor gene, we used 1) positional cloning and 2) subtraction technique. The delection site that it was regarded as 7q11.22 at first understood that it was 7q11.21 by comparison with bulletin of newly reported draft sequence. OS-4 gene regarded as a candidate important more at first was not included in this draft sequence. We gave priority to the 6-8 clone that draft sequence included array and analyzed it. Among ten kinds of gene which there is in common deletion region of 7q11.21 of choriocarcinoma, 6-8 clone is included in array given a presentation in draft sequence. This was gene having KRAB domain and Zn finger domain in human teratocarcinoma finger (HTF) 12 gene. HTF12 gene was conjugated by in full length vector plasmid and was introduced into choriocarcinoma cell strain. By induction, becoming gigantic of cell occurred, and cell mass culturing deteriorated. The syndesis ability of cell did not change very much. Cell fusion … More begins in induction cell. It was accompanied with deterioration with becoming gigantic of cell. Three kinds of splicing variants produced by a difference of promotor. By both induction, cell propagation was restrained. It was HTF12-2 that used for induction this time. It was each a thing on the basis of a difference of number of domain of Zn finger domain in HTF12-1 that appeared in normal placental villus. On this account it was estimated that the KRAV domain which there was in 5' site participated in cell fusion, propagation inhibition. We understood that there was a lot of similar gene in homology analysis. In particular concern area provided in linkage analysis of familial hydatidiform mole on the chromosome 19 has near by existing ZF1 gene and homology of 80%. The gene expression of ZF1 is recognized both in placenta and choriocarcinoma, and a difference of the work attracts attention.NECC1 provided by subtraction technique was gene provided than human gingival cDNA library. It was thought with the gene which contributed to deterioration of cell, and I thought that I participated in the legalization of villous trophoblast cell. When villous cytotrophoblast cell became the syncytium cell which fused, marker such as HPL, CSH expressed, but it was immunohistochmestrical that marker of similar expressed, and it was proved, and what I produced in mechanism same as syncitionization was estimated. This NECC1 understood gene only for homeobox needed in case of incidence of mouse, a thing same as HOP. Retrieval in placenta is not considered to be it. Less

为了分离绒毛膜癌抑制基因，我们采用了1）定位克隆和2）消减技术。最初认为是7q11.22的缺失位点，经与新报道的草图序列比较，确定为7q11.21。OS-4基因最初被认为是一个更重要的候选基因，但未被包括在该序列草案中。我们将序列草图中的6-8个克隆优先纳入阵列并进行分析，在绒毛膜癌7q11.21共同缺失区的10种基因中，6-8个克隆被纳入阵列，并在序列草图中进行了展示。这是人畸胎瘤指（HTF）12基因中具有KRAB结构域和Zn指结构域的基因。将HTF 12基因与全长载体质粒连接，导入绒毛膜癌细胞株。通过诱导，发生细胞变大，并且细胞团培养恶化。细胞的结合能力变化不大。细胞融合 ...更多信息 从诱导细胞开始。随着细胞体积的增大，细胞的退化也随之发生。不同启动子产生的三种剪接变体。通过这两种诱导，细胞增殖受到抑制。本次采用HTF 12 -2进行诱导。这是基于HTF 12 -1的锌指结构域在正常胎盘绒毛中出现的数目差异而产生的。据此推测，KRAV 5'端的结构域参与细胞融合、增殖抑制。通过同源性分析可知，在这些基因中存在着大量的相似基因。特别值得关注的是家族性葡萄胎19号染色体上的连锁分析所提供的区域与现有的ZF 1基因有近80%的同源性。ZF 1基因在胎盘和绒毛膜癌组织中均有表达，但差异性较大，利用差减技术获得的NECC 1基因与人牙龈cDNA文库相比，差异性较大。这是认为与基因导致细胞的恶化，我认为我参与了绒毛滋养层细胞的合法化。当绒毛细胞滋养层细胞成为融合的合胞体细胞时，HPL、CSH等标记物表达，但相似标记物的表达是特异性的，并证明了这一点，并估计了其产生的机制与合胞体细胞相同。该NECC 1仅理解小鼠发病情况下所需的同源框基因，与HOP相同。在胎盘检索不被认为是它。减

项目成果

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