Activation of MAP kinases by 5-fluorouracil in a 5-fluorouracil-resistant variant human cell line derived from a KT breast cancer cell line.
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.
Wu
Y
Y
Department of Biochemistry, School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Hiwasa
T
T
Isogai
E
E
Sonoda
T
T
Kita
K
K
Chen
Z
Z
Sugaya
S
S
Yamamori
H
H
Tanzawa
H
H
Suzuki
N
N
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
D000964:Antimetabolites, Antineoplastic; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005472:Fluorouracil