Details

Autor(en) / Beteiligte

• Vilaboa, Nuria E.
• Galán, Alba
• Troyano, Alfonso
• de Blas, Elena
• Aller, Patricio

Titel

Regulation of Multidrug Resistance 1 (MDR1)/P-glycoprotein Gene Expression and Activity by Heat-Shock Transcription Factor 1 (HSF1)

Ist Teil von

• The Journal of biological chemistry, 2000-08, Vol.275 (32), p.24970-24976

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2000

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Infection of HeLa cells with adenovirus-carrying HSF1+ cDNA, which encodes a mutated form of HSF1 with constitutive transactivation capacity, increased multidrug resistance 1 (MDR1) mRNA level and P-glycoprotein (P-gp) cell surface content and stimulated rhodamine 123 accumulation and vinblastine efflux activity. On the other hand, infection with adenovirus-carrying HSP70 andHSP27 cDNAs did not increase MDR1/P-gp expression. HSF1 regulates MDR1/P-gp expression at the transcriptional level, since HSF1+ bound the heat-shock consensus elements (HSEs) in the MDR1 gene promoter and also activated the expression of an MDR1 promoter-driven reporter plasmid (pMDR1(−1202)). In addition, heat-shock increased pMDR1(−1202) promoter activity but not the activity of a similar reporter plasmid with point mutations at specific HSEs, and the heat-induced increase was totally inhibited by co-transfection with an expression plasmid carrying HSF1−, a dominant negative mutant of HSF1. The stress inducers arsenite, butyrate, and etoposide also increased pMDR1(−1202) promoter activity, but the increase was not inhibited (in the case of butyrate) or was only partially inhibited (in the case of arsenite and etoposide) by HSF1−. These results demonstrate that HSF1 regulates MDR1 expression, and that the HSEs present in the −315 to −285 region mediate the heat-induced activation of the MDR1 promoter. However, other factors may also participate in MDR1 induction by stressing agents.