Abstract
background
It is believed that the main cause of carcinogenesis is the accumulation of DNA damage and mutations in oncogene or tumor suppressor gene. However the mutation frequency is too low to explain the cancer development. On the other hand, it is well known that there are some aneuploid cells in tumor cells, suggesting the involvement of aneuploidy on cancer development. However we don't know whether aneuploidy is main cause of carcinogenesis or not. Here we established the aneuploid cells in which a human chromosome has been introduced artificially, and analyzed the cells focused on the phenotypes of the carcinogenesis.
material and method
We used immortalized adult human mesenchymal stem cells, and established three aneuproid cell lines by microcell-mediated chromosome transfer method (each contains exogeneous human chromosome #1, #7 and #8). We used the cells containing only drug resistance gene as a control cell line. We examined cell growth, anchorage-independent growth as a marker of carcinogenesis in these cell lines, and also analyzed the abnormality of chromosome number and micronuclei yields in aneuploid cells.
results
Although no significant differences were observed on cell growth rate among cell lines, we observed that the aneuplid cells were unstable for the maintenance of the chromosome number. Moreover, the anchorage-independent growth in aneuplid cells were 1.5-fold higher than that in the control cells. These results suggest that the artificial aneuploid by the introduction of one chromosome in human cells cause the disruption of the maintenance mechanism for the stable chromosome number, and this instability may be leading to carcinogenesis.
