Mutation in p53 and de-regulation of p53-related gene expression in three human cell lines immortalized with 4-nitroquinoline 1-oxide or 60Co gamma rays
✍ Scribed by Mikio Itjima; Koichiro Mihara; Tadashi Kondo; Toshiya Tsuji; Chikashi Ishioka; Masayoshi Namba
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 739 KB
- Volume
- 66
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
IMMORTALIZED In vitro models of malignant transformation of human cells may provide considerable insight into the mechanisms of multistep carcinogenesis. It is well established that normal human cells must be immortalized before they can be malignantly transformed; however, they are stringently destined for aging and are rarely immortalized. The mechanism of cellular aging and immortalization is still unknown. We detected expression of only mutated p53 mRNA by direct sequencing of the revenetranscribed mRNA in 3 human cell lines immortalized either with 4-nitroquinoline I -oxide or with "CO gamma rays. Consequently, only the mutated p53 protein was expressed in each immortalized cell line. The expression of sdi I lp2 I and mdm2, both of which are positively regulated by wild-type p53, was significantly down-regulated in the immortalized cell lines, resulting in over-expression of cdk2 and cdk4. Introduction of the sdi I lp2 I gene into these cells was followed by a remarkable decrease in their ability to synthesize DNA. These results indicate that the p53 cascade may play an important role in the immortalization of human cells.