title: Activation of MAP kinases by 5-fluorouracil in a 5-fluorouracil-resistant variant human cell line derived from a KT breast cancer cell line.
abstract: To investigate the mechanism of the acquired resistance of human cells to an anticancer drug, 5-fluorouracil (5-FU), a drug-resistant clone, KTFU-4, was isolated from a human KT breast carcinoma cell line, treated with ethylmethanesulfonate and then with 5-FU. The viability of the KT cells, analyzed using an MTT assay, was suppressed by 5-FU in a dose-dependent manner, while that of the KTFU-4 cells was enhanced by it at concentrations between 0.1 and 1.0 microgram/ml. Treatment of KTFU-4 cells with 5-FU resulted in increased amounts of activated phosphorylated ERK1/2 and p38 MAP kinases, but not in the parent KT cells. It is thus possible that 5-FU stimulated the proliferation of KTFU-4 cells by activating a signal transduction pathway leading to cell growth.
authors.affiliation: Department of Biochemistry, School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: T
authors.initials: T
authors.lastname: Hiwasa
authors.forename: E
authors.initials: E
authors.lastname: Isogai
authors.forename: T
authors.initials: T
authors.lastname: Sonoda
authors.forename: K
authors.initials: K
authors.lastname: Kita
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Sugaya
authors.forename: H
authors.initials: H
authors.lastname: Yamamori
authors.forename: H
authors.initials: H
authors.lastname: Tanzawa
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005472:Fluorouracil