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Analysis of Gene Amplification in Association with Carcinogenesis

基因扩增与癌变相关的分析

基本信息

批准号：
03454169
负责人：
FUKUMOTO Manabu
金额：
$ 3.2万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

1. Overexpression of the c-myc gene in serous adenocarcinoma especially at stage III was significant, suggesting that the c-myc gene plays an important role for tumorigenesis of ovarian cancer at later stages.2. The structure and location of amplicons in two independent cell lines which have coamplification of the c-myc and the Ki-ras genes were analyzed. Each one of amplicons shared one chromosome in both the cell lines. We conclude that amplification of copy number occurred in a form of episome and these two independent amplified genes got associated at chromosomal level by a common mechanism.3. Amplification of either c-myc, erbB or bcl-1 gene was found in more than 50% or human esophageal carcinoma cell lines. The incidence of coamplification of the c-myc gene and other genes was significant. Although bcl-1 gene amplification was found in 39% of cell lines, its expression is undetectable in one cell line. The bcl-1 gene is mapped to the chromosomal locus 11q13 where several oncogenes form cluster. Therefore, the investigation whether there is a target gene which is overexpressed in the amplicon is ongoing.4. An autocrine mechanism through basic fibroblast growth factor we applied neutralizing antibody against bFGF to inhibit growth of glioma cells by blocking the autocrine mechanism. This strategy would be a potential therapy to control gliomas.

1.c-myc基因在卵巢浆液性腺癌中的过度表达，尤其是在III期，提示c-myc基因在晚期卵巢癌的发生发展中起重要作用。分析了c-myc和Ki-ras基因共扩增的两个独立细胞系的扩增产物的结构和位置。在两个细胞系中，每个扩增片段共享一条染色体。我们得出的结论是，拷贝数的放大是以Episome的形式发生的，这两个独立的扩增基因在染色体水平上通过共同的机制联系在一起。C-myc、erbB或bcl1基因扩增在50%以上的人食道癌细胞系中均有扩增。C-myc基因与其他基因共扩增的发生率显著。虽然在39%的细胞系中检测到bcl1基因的扩增，但在一株细胞系中未检测到其表达。Bcl-1基因被定位在染色体11q13上，在该位置上有多个癌基因形成簇。因此，对扩增产物中是否存在过表达的目的基因的研究正在进行中。通过碱性成纤维细胞生长因子的自分泌机制我们应用了抗碱性成纤维细胞生长因子的中和抗体，通过阻断自分泌机制来抑制胶质瘤细胞的生长。这一策略将是控制胶质瘤的一种潜在疗法。