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1. Biochem Biophys Res Commun. 2012 Mar 24. [Epub ahead of print]

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

Hegedüs C, Truta-Feles K, Antalffy G, Brózik A, Kasza I, Német K, Orbán TI,
Ozvegy-Laczka C, Váradi A, Sarkadi B.

Membrane Research Group of the Hungarian Academy of Sciences, Department of
Biophysics, Semmelweis University and National Blood Center, Budapest, Hungary.

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.

Copyright © 2012. Published by Elsevier Inc.

PMID: 22449574 [PubMed - as supplied by publisher]