PI3-kinase and mTOR inhibitors differently modulate the function of the ABCG2 multidrug transporter |
| |
Authors: | Hegedüs Csilla Truta-Feles Krisztina Antalffy Géza Brózik Anna Kasza Ildikó Német Katalin Orbán Tamás I Özvegy-Laczka Csilla Váradi András Sarkadi Balázs |
| |
Institution: | Membrane Research Group of the Hungarian Academy of Sciences, Department of Biophysics, Semmelweis University and National Blood Center, Budapest, Hungary. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|