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Updated: May 20, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

Resistance to the mTOR-inhibitor RAD001 elevates integrin α2- and β1-triggered motility, migration and invasion of

I Tsaur1, J Makarević, E Juengel

  • 1Department of Urology, Goethe-University, Frankfurt am Main 60590, Germany.

British Journal of Cancer
|July 12, 2012
PubMed
Abstract

Insights

Chronic RAD001 treatment for prostate cancer can lead to resistance by increasing cell motility. This resistance is linked to changes in integrin expression, driving tumor cell movement and potential metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Mammalian target of rapamycin (mTOR) inhibitors show promise for advanced prostate cancer.
  • Chronic exposure to mTOR inhibitors can induce drug resistance, limiting their therapeutic efficacy.

Purpose of the Study:

  • To investigate the metastatic potential of prostate cancer cells resistant to the mTOR inhibitor RAD001.
  • To elucidate the molecular mechanisms underlying RAD001 resistance in prostate cancer.

Main Methods:

  • Assessed adhesion, motility, migration, and invasion of RAD001-susceptible (PC3(par)) and RAD001-resistant (PC3(res)) prostate cancer cells.
  • Analyzed integrin expression profiles (α and β subtypes) using flow cytometry, western blotting, and real-time PCR.
  • Determined the activation status of integrin-related signaling pathways, including EGFR, Akt, p70S6kinase, and ERK1/2.

Main Results:

  • PC3(res) cells exhibited reduced adhesion but enhanced motility, migration, and invasion compared to PC3(par) cells.
  • Integrin expression significantly changed in PC3(res) cells, with elevated α2 and β1, and reduced α1, α6, and α5 subtypes.
  • Akt signaling pathway activation was upregulated in PC3(res) cells, and blocking α2 and β1 integrins reduced tumor cell motility.

Conclusions:

  • Chronic RAD001 treatment induces resistance in prostate cancer cells.
  • Resistance is characterized by altered integrin expression, promoting increased cell motility.
  • Targeting specific integrins may offer strategies to overcome RAD001 resistance in prostate cancer.

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