Abstract
Aneuploidy or chromosome imbalance is the most massive genetic abnormality of cancer cells. It used to be considered the cause of cancer when it was discovered more than 100 years ago. Since the discovery of the gene, the aneuploidy hypothesis has lost ground to the hypothesis that mutation of cellular genes causes cancer.
Here we examine the aneuploidy hypothesis in view of the fact that nearly all solid cancers are aneuploid, that many carcinogenesis are nongenotoxic, and that mutated genes from cancer cells do not transform diploid human or animal cells.
In this study, we used the primary cells derived from 13-days embryo of C57BL mouse with or without p53 gene functions. Cells were subcultured every 5-day at 106 cells per 752cm culture flask. Both p53 (+/+) and p53 (-/-) cells were spontaneously immortalized, but only p53 (-/-) cells became tumorigenic. All of tumorigenic cells were aneuploid. Instability of chromosome of p53 (-/-) cells was greater than that of p53 (+/+) cells. On the other hand, non-tumorigenic cells were tetraploid, it was stable.
Considering these results, we conclude that aneuploidy is the cause rather than a consequence of transformation.
