Regulation of the MDR1 promoter by cyclic AMP-dependent protein kinase and transcription factor Sp1.
Regulation of the MDR1 promoter by cyclic AMP-dependent protein kinase and transcription factor Sp1.
复制标题
DOI：
10.3892/ijo.12.2.383
复制
发表时间：
1998-02
影响因子：
5.2
通讯作者：
C. Rohlff;R. Glazer
中科院分区：
文献类型：
--
作者：
C. Rohlff;R. Glazer
乳腺癌细胞系MCF-7/ADR 50的多药耐药（MDR）主要依赖于MDR 1基因的转录激活。我们现在报告，MDR在这个细胞系是部分逆转的I型cAMP依赖性蛋白激酶（PKA）抑制剂，8-Cl-cAMP。MDR 1启动子活性也通过PKA依赖性途径调节，并被8-Cl-cAMP抑制，并被对映体激动剂SpcAMP刺激[S]。通过Sp1反应元件的MDR 1启动子活性被外源性Sp1刺激，我们已经证明该因子被PKA激活。这些结果表明，MDR 1启动子活性与cAMP/PKA信号通路，PKA拮抗剂可能是有用的逆转多药耐药表型。
The expression of multidrug-resistance (MDR) in breast carcinoma cell line MCF-7/ADR50 is primarily dependent on the transcriptional activation of the MDR1 gene. We now report that MDR in this cell line is partially reversed by the type I cAMP-dependent protein kinase (PKA) inhibitor, 8-Cl-cAMP. MDR1 promoter activity was also regulated through a PKA-dependent pathway and was inhibited by 8-Cl-cAMP, and stimulated by the enantiomeric agonist, SpcAMP[S]. MDR1 promoter activity through an Sp1 response element was stimulated by exogenous Sp1, a factor that we have shown to be activated by PKA. These results indicate that MDR1 promoter activity is linked to the cAMP/PKA signaling pathway, and that PKA antagonists may be useful for reversing the multidrug-resistant phenotype.