Involvement of heat shock factor in regulating transcriptional activation of MDR1 gene in multidrug-resistant cells

被引:30
作者
Kim, SH [1 ]
Hur, WY [1 ]
Kang, CD [1 ]
Lim, YS [1 ]
Kim, DW [1 ]
Chung, BS [1 ]
机构
[1] CHANG WON UNIV,DEPT MICROBIOL,CHANG WON 641241,SOUTH KOREA
关键词
HSF; MDR1; gene; heat shock protein; H-87; multidrug-resistant cells;
D O I
10.1016/S0304-3835(97)04725-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The present study provides evidence that heat shock factor (HSF) may be involved in a transacting factor modulating multidrug resistance 1 (MDR1) gene. In conjunction with the presence of several heat shock elements (HSEs) in the 5' region of the MDR1 gene, we compared the level of HSF which binds to HSEs in multidrug-resistant P388/M and FM3A/M cells with that in their parental counterparts. Under unstressed condition, these multidrug-resistant cells showed constitutive HSF DNA-binding activity in the nucleus of the cells, whereas their parental counterparts did not show detectable HSF DNA-binding activity. We found that H-87, protein kinase A inhibitor, inhibited HSF DNA-binding activity in heat-shocked P388/M cells and also suppressed the levels of hsp90 and hsp70. These results demonstrated that HSF might be an important transcriptional regulator for inducing MDR1 gene, and modulation of HSF activity might be a useful potential target for reversing MDR. (C) 1997 Elsevier Science Ireland Ltd.
引用
收藏
页码:9 / 14
页数:6
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