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Mutation in p53 and de‐regulation of p53 ‐related gene expression in three human cell lines immortalized with 4‐nitroquinoline 1‐oxide or 60 Co gamma rays
Author(s) -
Itjima Mikio,
Mihara Koichiro,
Kondo Tadashi,
Tsuji Toshiya,
Ishioka Chikashi,
Namba Masayoshi
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960529)66:5<698::aid-ijc19>3.0.co;2-0
Subject(s) - immortalised cell line , cell culture , carcinogenesis , biology , transfection , microbiology and biotechnology , gene , mutation , gene expression , 4 nitroquinoline 1 oxide , cell , mdm2 , cancer research , genetics
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 reverse‐transcribed mRNA in 3 human cell lines immortalized either with 4‐nitroquinoline 1‐oxide or with 60 Co gamma rays. Consequently, only the mutated p53 protein was expressed in each immortalized cell line. The expression of sdi I/ p 21 and mdm 2, both of which are positively regulated by wild‐type p 53, was significantly down‐regulated in the immortalized cell lines, resulting in over‐expression of cdk2 and cdk4. Introduction of the sdi I/ p 21 gene into these cells was followed by a remarkable decrease in their ability to synthesize DNA. These results indicate that the p 53 cascade may play an important role in the immortalization of human cells. © 1996 Wiley‐Liss, Inc.