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 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.
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 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.
Authors: Helen A Foster; Julie Davies; Ryan C Pink; Serife Turkcigdem; Anastasia Goumenou; David R Carter; Nigel J Saunders; Peter Thomas; Emmanouil Karteris Journal: J Steroid Biochem Mol Biol Date: 2013-03-26 Impact factor: 4.292
Authors: B K Nayak; D Feliers; S Sudarshan; W E Friedrichs; R T Day; D D New; J P Fitzgerald; A Eid; T Denapoli; D J Parekh; Y Gorin; K Block Journal: Oncogene Date: 2012-08-06 Impact factor: 9.867