PI3-kinase and mTOR inhibitors differently modulate the function of the ABCG2 multidrug transporter

详细信息	查看全文 | 推荐本文 |

• 作者：Csilla Heged&uuml ; s^a ; ¹ ; Krisztina Truta-Feles^a ; ¹ ; Gé ; za Antalffy^a ; Anna Bró ; zik^b ; Ildikó ; Kasza^a ; Katalin Né ; met^a ; Tamá ; s I. Orbá ; n^a ; Csilla Ö ; zvegy-Laczka^a ; Andrá ; s Vá ; radi^b ; Balá ; zs Sarkadi^a ; ^c ; ^{sarkadi@biomembrane.hu}
• 关键词：ABC ; ATP-binding cassette ; PI3K ; phosphatidylinositol 3-kinase ; mTOR ; mammalian target of rapamycin ; MDR ; multidrug resistance
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：20 April, 2012
• 卷：420
• 期：4
• 页码：869-874
• 文件大小：683 K

摘要

The ATP-binding cassette (ABC) transporter ABCG2 plays an important role in tissue detoxification and confers multidrug resistance to cancer cells. Identification of expressional and functional cellular regulators of this multidrug transporter is therefore intensively pursued. The PI3-kinase/Akt signaling axis has been implicated as a key element in regulating various cellular functions, including the expression and plasma membrane localization of ABCG2. Here we demonstrate that besides inhibiting their respective target kinases, the pharmacological PI3-kinase inhibitor LY294002 and the downstream mTOR kinase inhibitor rapamycin also directly inhibit ABCG2 function. In contrast, wortmannin, another commonly used pharmacological inhibitor of PI3-kinase does not interact with the transporter. We suggest that direct functional modulation of ABCG2 should be taken into consideration when pharmacological agents are applied to dissect the specific role of PI3-kinase/Akt/mTOR signaling in cellular functions.