Molecular Pathology of Solid Tumors in Childhood
儿童实体瘤的分子病理学
基本信息
- 批准号:10307004
- 负责人:
- 金额:$ 24.64万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (A)
- 财政年份:1998
- 资助国家:日本
- 起止时间:1998 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We performed molecular pathological analysis of embryonal tumors such as germ cell tumors, Wilms tumors and Ewing/PNET tumors which are thought to be derived from embryonal tissue during.1, we originally isolated EAT (early gene induced by all trans retinoic acid) gene from embryonal carcinoma cell lines (NCR-G3). Sequencing analysis revealed that EAT possessed BH1 and BH2 domains suggesting a bcl family gene. This gene was shown to have antiapoptotic functions by vitro and in vivo studies. Northern analysis and immunohistochemical studies disclosed that he EAT gene distributed in a variety of fetal and adult tissues including stage of early embryogenesis. EAT gene was shown to exclusively localize in the external and internal membrane of mitochondria by using immunoelectron microscopic procedures. These findings suggested that this gene play an important role in maintenance of early embryogenesis through antiapoptotic functions.2, Wilms tumor are a typical embryonal tumors that is der … More ived from metanephric blastoma and the most common renal tumors in childhood. Novel gene, WT1, has been isolated chromosome11p13 region as a responsible gene in oncogenesis of Wilms tumor. This gene also play an important role in normal nephrogenesis and gonadal developments, especially male genital organs. Denys-Drash syndrome characterized by association of Wilms tumor, early onset and progressive renal failure and urogenital anomalies. Recent studies showed that exonic mutations at zinc finger domains of WT1 is responsible for pathogenesis of this syndrome. We analyzed WT1 mutations in 18 clinically diagnosed "Denys-Drash"(Drash) syndrome cases. 9 cases were typical Drash syndrome. Whereas another cases showed inronic point mutations at the splicing donor site at exon9. These mutations affect alternative splicing. The isoforms retaining three amino acids, KTS, are not produced. Clinical features of the patients with the intronic mutations correlated well with those of Frasier syndrome, characterized by more slowly progressing nephropathy than Denys-Drash syndrome, associated streak gonads and no development of Wilms' tumor. Our results indicate that WT1 isoforms with or without KTS have different functions in tumorigenesis and organogenesis of kidneys and gonads. Less
1.我们首次从胚胎癌细胞系(NCR-G3)中分离出EAT(全反式维甲酸诱导的早期基因)基因。序列分析表明,EAT具有BH1和BH2结构域,提示该基因为bc1家族基因。体外和体内研究表明该基因具有抗细胞凋亡的功能。Northern分析和免疫组织化学研究表明,该基因分布于胎儿和成人的多种组织中,包括早期胚胎发育阶段。用免疫电子显微镜技术证明EAT基因定位于线粒体的外膜和内膜。这些发现提示该基因通过抗细胞凋亡功能在维持早期胚胎发育中起重要作用。2、肾母细胞瘤是一种典型的胚胎性肿瘤,属于DER…。更多的人来自后肾母细胞瘤和最常见的儿童肾脏肿瘤。新基因WT1已被克隆到染色体11p13区,是肾母细胞瘤发生的重要致病基因。该基因在正常肾脏发生和性腺发育,特别是男性生殖器官发育中也起着重要作用。Denys-Drash综合征的特征是肾母细胞瘤、早期发病和进行性肾功能衰竭以及泌尿生殖系统异常。最近的研究表明,WT1锌指域的外显子突变与本综合征的发病有关。我们分析了18例临床诊断为“Denys-Drash”(Drash)综合征的WT1突变。9例为典型的Drash综合征。而另一例则在外显子9的剪接供体部位发生了点突变。这些突变会影响选择性剪接。不产生保留三个氨基酸KTS的异构体。内含子突变患者的临床特征与Frasier综合征有很好的相关性,表现为比Denys-Drash综合征进展更慢的肾病,相关的条纹性腺和无肾母细胞瘤的发展。我们的结果表明,WT1亚型在肾和性腺的肿瘤发生和器官发生中具有不同的功能。较少
项目成果
期刊论文数量(54)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Ando T, Hata J, et al.: "EAT/mcl-1,a Member of the bcl-2 Related Genes, Confers Resistance to Apoptosis Induced by cis-Diamine"Jpn J Cancer Res. 89. 1326-1333 (1998)
Ando T、Hata J 等人:“EAT/mcl-1,bcl-2 相关基因的成员,赋予对顺式二胺诱导的细胞凋亡的抵抗力”Jpn J Cancer Res。
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Makino S, Hata J, et al.: "Cardiomyocytes can be generated from marrow stromal cells in vitro"J Clin Invest. 103. 697-705 (1999)
Makino S、Hata J 等人:“心肌细胞可以在体外由骨髓基质细胞产生”J Clin Invest。
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Matsushita K, Hata J, et al.: "The EAT/mcl-1 gene, an inhibitor of apoptosis, is up-regulated in the early stage of acute myocardial infarction"BBA. 1472. 471-478 (1999)
Matsushita K、Hata J 等人:“EAT/mcl-1 基因是细胞凋亡的抑制剂,在急性心肌梗死的早期阶段上调”BBA。
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Kinjo K, Hata J, et al.: "Arsenic trioxide (As2O3)-induced apoptosis and differentiation in retinoic acid-resistant acute promyelocytic leukemia model in hGM-CSF-producing transgenic SCID mice"Leukemia. 14. 431-438 (2000)
Kinjo K、Hata J 等人:“在产生 hGM-CSF 的转基因 SCID 小鼠中,三氧化二砷 (As2O3) 诱导的视黄酸耐药急性早幼粒细胞白血病模型中的细胞凋亡和分化”白血病。
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Fukushima,S.: "Augmentation of human leukemic cell invasion by the activation of small GTP-binding protein Rho"Expt Hematol. (in press). (2000)
Fukushima,S.:“通过激活小 GTP 结合蛋白 Rho 增强人类白血病细胞的侵袭”Expt Hematol。
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HATA Jun-ichi其他文献
HATA Jun-ichi的其他文献
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{{ truncateString('HATA Jun-ichi', 18)}}的其他基金
Establishment of neuroblastoma regression model and molecular mechanisms
神经母细胞瘤消退模型的建立及分子机制
- 批准号:
14570164 - 财政年份:2002
- 资助金额:
$ 24.64万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of novel humanized-mice and application to regenerative medicine
新型人源化小鼠的研制及其在再生医学中的应用
- 批准号:
12357002 - 财政年份:2000
- 资助金额:
$ 24.64万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Molecular and Cell Biological Differentiation Capabilities on Human Germ Cell Tumor Cells
人类生殖细胞肿瘤细胞的分子和细胞生物分化能力
- 批准号:
03454174 - 财政年份:1991
- 资助金额:
$ 24.64万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
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The study of combination immunotherapy of Wilms' Tumor 1 (WT1) peptide vaccine in pediatric brain tumor
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