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Participation of mTOR in the regulation of multidrug resistance of tumor cells

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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Molecular mechanisms of the influence of PI3K/Akt/PTEN/mTOR-signaling pathway on survival of tumor cells treated with cytotoxic drugs was studied using rapamycin (Rapa), mTOR specific inhibitor, and 9 human tumor cell lines of different origin and with different Akt kinase activity. Three of these cell lines were selected for drug resistance due to P-glycoprotein (Pgp or ABCB1) overexpression. Rapa inhibited phosphorylation of mTOR downstream effectors. Rapa sensitivity of the cells was Akt-dependent but did not correlate with ABCB1 overexpression. Suppression of mTOR function increased drug resistance in 8 out of 9 cell lines studied. The influence of Rapa on the ABC-transporter gene expression was examined. It was shown that in half of the cell lines studied Rapa exerted differential effects on the amount of ABC-transporter proteins: in some cases the protein amount decreased and in others, increased. The amount of mRNA remained unchanged. These data suggest that mTOR can regulate ABC transporters at the level of translation.

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Authors and Affiliations

  1. Institute of Carcinogenesis, Blokhin Cancer Research Center, Kashirskoe shosse, 24, Moscow, 115478, Russia

    E. A. Scherbakova, E. Yu. Rybalkina, T. P. Stromskaya & A. A. Stavrovskaya

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  1. E. A. Scherbakova
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  2. E. Yu. Rybalkina
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  3. T. P. Stromskaya
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  4. A. A. Stavrovskaya
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Correspondence to E. Yu. Rybalkina.

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Original Russian Text © E.A. Scherbakova, E.Yu. Rybalkina, T.P. Stromskaya, A.A. Stavrovskaya, 2009, published in Biologicheskie Membrany, 2009, Vol. 26, No. 2, pp. 119–125.

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Scherbakova, E.A., Rybalkina, E.Y., Stromskaya, T.P. et al. Participation of mTOR in the regulation of multidrug resistance of tumor cells. Biochem. Moscow Suppl. Ser. A 3, 184–189 (2009). https://doi.org/10.1134/S1990747809020111

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  • DOI: https://doi.org/10.1134/S1990747809020111

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