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

Helen Foster1, Helen M Coley, Anastasia Goumenou

  • 1Centre for Cell Chromosome Biology, Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge UB8 3PH, UK. Emmanouil.karteris@brunel.ac.uk

Anticancer Research
|October 15, 2010
PubMed
Abstract

Insights

Drug resistance in ovarian cancer is a challenge. This study found that the mammalian target of rapamycin (mTOR) pathway may be involved in paclitaxel resistance, suggesting potential new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Drug resistance limits the efficacy of cancer chemotherapy.
  • The mammalian target of rapamycin (mTOR) pathway is often upregulated in advanced ovarian cancer.
  • Inhibiting the mTOR pathway has shown potential to enhance chemosensitivity in ovarian cancer cell lines.

Purpose of the Study:

  • To investigate the expression of DEPTOR, mTOR, RICTOR, RAPTOR, and S6 kinases.
  • To compare protein expression in paclitaxel-sensitive and paclitaxel-resistant ovarian cancer cell lines (SKOV-3 and PEO1).

Main Methods:

  • Quantitative and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).
  • Immunofluorescent analysis.
  • Western blotting.

Main Results:

  • DEPTOR was significantly upregulated in both paclitaxel-resistant cell lines.
  • Differential expression of RICTOR, RAPTOR, and mTOR was observed between the two resistant cell lines.
  • Changes in p70S6K splice variants and phosphorylation were noted, with cell-type specificity.

Conclusions:

  • The mammalian target of rapamycin (mTOR) signaling pathway is hypothesized to play a role in mediating paclitaxel resistance in ovarian cancer.
  • Understanding these molecular changes could lead to strategies to overcome drug resistance.

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