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Induction of efficient apoptosis and cell‐cycle arrest in tumor cells by adenovirus‐mediated p53 A4 mutant
Author(s) -
Maeda Akihiro,
Nakamura Seiichi,
Isono Masato,
Osaki Mitsuhiko,
Ito Hisao,
Sato Kenzo
Publication year - 2006
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2006.01934.x
Subject(s) - multiplicity of infection , apoptosis , hela , biology , mutant , cell cycle , cell cycle checkpoint , cancer research , microbiology and biotechnology , cell culture , carcinogenesis , dna fragmentation , programmed cell death , cell , tumor suppressor gene , cancer cell , cancer , gene , genetics
p53 is an effective tumor suppressor and is inactivated in numerous cancer cells. In the present study, p53 mutant A4, which carries mutations in C‐terminus of the protein and is resistant to murine double minute 2‐mediated degradation, was exploited to introduce p53 function in tumor cells. The effect of p53 A4 mutant with recombinant adenovirus vector (Ad‐p53 A4) was examined. Ad‐p53 A4 infection at a low multiplicity of infection showed significant accumulation of p53 protein and strongly induced a killing effect on osteosarcoma cell line MG‐63 that is less sensitive to transduction of wild‐type p53 . DNA fragmentation assay and caspase assay showed that the cell death induced by Ad‐p53 A4 was more rapid and higher than that by Ad‐p53 wild‐type infection. It is also showed Ad‐p53 A4 induces cell‐cycle arrest in G1 phase. Moreover, a similar effect was observed in some human cancer cell lines (HeLa, HepG2, KATO III and Saos‐2) in various status of endogenous p53 expression. These results suggest that Ad‐p53 A4 has the ability to strongly suppress tumor cells and is a promising, novel tool for cancer gene therapy.