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Title: Differential expression of mTOR signalling components in drug resistance in ovarian cancer
Authors: Foster, H
Coley, HM
Goumenou, A
Pados, G
Harvey, AJ
Karteris, E
Keywords: Ovarian cancer;DEPTOR;mTOR;S6 kinase;Paclitaxel resistance
Issue Date: 2010
Publisher: The International Institute of Anticancer Research
Citation: Anticancer Research, 30(9): 3529 - 3534, Sep 2010
Abstract: Background/Aim: A limitation to successful cancer chemotherapy treatments is the acquisition of drug resistance. In advanced-stage ovarian cancer, the mammalian target of rapamycin (mTOR) pathway is upregulated, and inhibition of this pathway increases chemosensitivity in ovarian carcinoma cell lines. In this study, the expression of DEPTOR, mTOR, RICTOR, RAPTOR and S6 kinases were investigated in SKOV-3 and PEO1 parental and the paclitaxel-resistant (TaxR) SKOV-3TaxR and PEO1TaxR cell lines. Materials and Methods: RT-PCR, immunofluorescent analysis and Western blotting were carried out. Results: Quantitative RT-PCR revealed significant up-regulation of DEPTOR in both paclitaxel-resistant cell lines. SKOV-3TaxR exhibited down-regulation of RICTOR, RAPTOR and mTOR, whereas PEO1-TaxR showed down-regulation of RAPTOR and up-regulation of RICTOR and mTOR. Semi-quantitative RT-PCR analysis revealed marked changes in the expression of p70S6K splice variants mRNA in PEO1TaxR. Moreover, the phosphorylation status of p70S6K at Ser371 appears to be cell-type specific. Conclusion: We hypothesize that mTOR signalling may play a role in mediating paclitaxel resistance in ovarian cancer.
Description: This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2010 The International Institute of Anticancer Research.
ISSN: 0250-7005
Appears in Collections:Biological Sciences
Brunel OA Publishing Fund
Dept of Life Sciences Research Papers

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