title: Restoration of p53 gene function in 12-O-tetradecanoylphorbor 13-acetate-resistant human leukemia K562/TPA cells.
abstract: 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.
authors.affiliation: Pharmacology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Usuda
authors.forename: Motoko
authors.initials: M
authors.lastname: Inomata
authors.forename: Hisao
authors.initials: H
authors.lastname: Fukumoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Kuh
authors.forename: Kazuya
authors.initials: K
authors.lastname: Fukuoka
authors.forename: Harubumi
authors.initials: H
authors.lastname: Kato
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
mesh_terms: 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
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D013755:Tetradecanoylphorbol Acetate