Restoration of p53 gene function in 12-O-tetradecanoylphorbor 13-acetate-resistant human leukemia K562/TPA cells.
The human leukemia K562 cell line does not express wild-type p53 protein. Due to the loss of one p53 allele and an insertion mutation in exon 5 of the other allele resulting in a frameshift mutation, K562 cells express a truncated p53 protein of 148 amino acids. A human leukemia phorbol ester-resistant subline, K562/TPA, is cross-resistant to some anticancer agents. A remarkable difference in cell cycle progression at G1/S phase was observed in the synchronised K562/TPA cells as compared with K562 cells. Southern blot and DNA sequence analysis revealed no mutation in exon 5 of the p53 gene in K562/TPA cells. p21Cip1 expression was also restored in K562/TPA cells confirming that the reversal of this p53 gene mutation restored wild-type p53 function in these cells. This is a unique report describing reversal of p53 gene mutation by drugs. This was associated with the expression of wild-type p53 mRNA and protein in K562/TPA cells. The K562/TPA cell line may provide a very useful tool for the investigation of the relationship between p53 status and chemosensitization.
Usuda
Jitsuo
J
Pharmacology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Inomata
Motoko
M
Fukumoto
Hisao
H
Iwamoto
Yasuo
Y
Suzuki
Toshihiro
T
Kuh
Hyo-Jeong
HJ
Fukuoka
Kazuya
K
Kato
Harubumi
H
Saijo
Nagahiro
N
Nishio
Kazuto
K
D015139:Blotting, Southern; D002453:Cell Cycle; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D019008:Drug Resistance, Neoplasm; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D020014:K562 Cells / Q000187:drug effects* / Q000378:metabolism; D007621:Karyotyping; D017422:Sequence Analysis, DNA; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D013755:Tetradecanoylphorbol Acetate