Analysis of Gene Amplification in Association with Carcinogenesis

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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.