Differential expression of mTOR signalling components in drug resistance in ovarian cancer

  • Foster H
  • Coley H
  • Goumenou A
 et al. 
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Abstract

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 up- regulated, 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.

Author-supplied keywords

  • DEPTOR
  • Ovarian cancer
  • Paclitaxel resistance
  • S6 kinase
  • mTOR

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