Involvement of protein kinase in environmental stress‐induced activation of human multidrug resistance 1 (MDR1) gene promoter

FEBS Letters

Hidaka, Katsuhiko¹  Kuwano, Michihiko³  Tanimura, Hideyuki³  Abe, Hiroko³  Uchida, Yuzo²  Uchiumi, Takeshi³  Kohno, Kimitoshi³  Asakuno, Keizo³ 

[1] Department of Surgery, Saga Medical School, Nabeshima, Saga 849, Japan;Department of Surgery, Oita Medical University, Hasama-machi, Oita 879-55, Japan;Departments of Biochemistry and Surgery, Oita Medical University, Hasama-machi, Oita 879-55, Japan

关键词: Multidrug resistance 1 gene;    H-7;    Okadaic acid;    Ultraviolet light;    MDR1;    multidrug resistance 1;    UV;    ultraviolet light;    EMS;    ethyl methane sulfonate;    CAT;    chloramphenicol acetyltransferase;    5-FU;    5-fluorouracil;    TPA;    12-O-tetradecanoylphorbol-13-acetate;    RT-PCR;    reverse transcription-polymerase chain reaction;   

DOI  :  10.1016/0014-5793(93)81750-T

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The human MDR1 gene can be induced in response to various environmental stimuli. To examine whether such stress-induced activation of the MDR1 gene can be modulated by protein kinase, we employed a stable human cancer KB cell line which contained the bacterial chloramphenicol acetyltransferase (CAT) gene directed by the MDR1 gene promoter. H-7, a protein kinase C inhibitor, at more than 40 μM inhibited activation of the MDR1 promoter that was induced by ethylmethane sulfonate, 5-fluorouracil or UV irradiation. DNA binding activity of nuclear factors recognizing the MDR1 promoter was augmented in KB cells treated with UV, but decreased in cells treated concomitantly with H-7. Okadaic acid alone was able to induce the promoter activation, and this induction was dependent on specific promoter sequences. Okadaic acid also enhanced the DNA binding activity of nuclear factors recognizing the MDR1 promoter. The phosphorylation of transacting factors may modulate the MDR1 gene promoter activity.

【 授权许可】

Unknown