Analysis of Gene Amplification in Association with Carcinogenesis

1. c-myc基因在浆液腺癌中，特别是在ⅲ期的过表达是显著的，这表明c-myc基因在卵巢癌晚期的肿瘤发生中起着重要的作用。分析了c-myc和Ki-ras基因共扩增的两种独立细胞系中扩增子的结构和位置。每个扩增子在两个细胞系中共享一条染色体。我们认为拷贝数的扩增是以偶发体的形式发生的，这两个独立的扩增基因在染色体水平上通过共同的机制相互关联。在50%以上的人食管癌细胞系中发现c-myc、erbB或bcl-1基因扩增。c-myc基因与其他基因共扩增的发生率显著。虽然在39%的细胞系中发现bcl-1基因扩增，但在一个细胞系中未检测到其表达。bcl-1基因定位于染色体位点11q13，在11q13上，多个致癌基因形成簇。因此，对扩增子中是否存在过表达的靶基因的研究仍在进行中。通过碱性成纤维细胞生长因子的自分泌机制我们应用抗bFGF的中和抗体通过阻断自分泌机制抑制胶质瘤细胞的生长。这种策略可能是控制神经胶质瘤的一种潜在疗法。

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.