Inhibition of Abcg2 transporter on primitive hematopoietic stem cells by All-trans retinoic acid increases sensitivity to anthracycline
Inhibition of Abcg2 transporter on primitive hematopoietic stem cells by All-trans retinoic acid increases sensitivity to anthracycline
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DOI：
10.2492/inflammregen.30.55
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发表时间：
2010-01
影响因子：
8.1
通讯作者：
Lawrence Lein;Y. Nagai;Y. Mabuchi;Sadafumi Suzuki;S. Morikawa;Y. Matsuzaki
中科院分区：
文献类型：
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作者：
Lawrence Lein;Y. Nagai;Y. Mabuchi;Sadafumi Suzuki;S. Morikawa;Y. Matsuzaki
全反式视黄酸（RA）调节多种组织和细胞类型的生长和分化。在这里，我们发现RA有一个新的作用，乳腺癌耐药蛋白（Abcg 2）抑制剂。RA，像转运抑制剂利血平，剂量依赖性地减少Hoechst染料从HSC流出抑制Abcg 2转运蛋白，而不需要新的转录。RA和利血平对SP的影响在洗脱后是可逆的。在稳定表达Abcg 2的NIH 3 T3-GFP细胞中获得了类似的结果。RA处理和Abcg 2缺陷的HSC显示出对多柔比星（一种蒽环类药物）的敏感性增加。我们的证据表明，除了在HSC的生存，生长和分化中发挥关键作用外，RA还具有作为Abcg 2转运蛋白抑制剂的新功能。
It is well established that All-trans retinoic acid (RA) regulates the growth and differentiation of a wide variety of tissues and cell types. Here we found that RA has a new role, the breast cancer resistance protein (Abcg2) inhibitor. RA, like the transporter inhibiter reserpine, dose-dependently reduced the efflux of Hoechst dye from HSCs by inhibiting the Abcg2 transporter without requiring new transcription. The effects of RA and reserpine on the SP were reversible upon wash-out. Similar results were obtained in NIH3T3-GFP cells stably expressing Abcg2. RA-treated and Abcg2-deficient HSCs showed increased sensitivity to doxorubicin, a type of anthracycline. Our evidence suggests that, besides playing crucial roles in the survival, growth, and differentiation of HSCs, RA has a novel function as an inhibitor of the Abcg2 transporter.