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Pre-clinical Orthotopic Murine Model of Human Prostate Cancer
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mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice

David A Guertin1, Deanna M Stevens, Maki Saitoh

  • 1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Cancer Cell
|February 3, 2009
PubMed

Insights

Mammalian target of rapamycin complex 2 (mTORC2) is essential for prostate cancer formation in PTEN-deficient cells. Inhibiting mTORC2 may offer a new therapeutic strategy for prostate cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The mammalian target of rapamycin (mTOR) pathway is a critical regulator of cell growth, proliferation, and survival.
  • mTOR signaling is frequently dysregulated in various cancers, including prostate cancer.
  • The specific role of mTOR complex 2 (mTORC2) in prostate cancer progression remains largely undefined.

Purpose of the Study:

  • To investigate the role of mTORC2 in prostate cancer development and progression.
  • To determine if mTORC2 is essential for tumor formation in PTEN-deficient prostate cancer models.
  • To evaluate the therapeutic potential of targeting mTORC2 in prostate cancer.

Main Methods:

  • Utilized PTEN-deficient human prostate epithelial cells and Pten heterozygous mouse models.
  • Injected transformed cells into nude mice to assess tumor formation.
  • Assessed the impact of Rictor gene dosage on prostate cancer development.
  • Investigated mTORC2 requirement in both normal and cancerous prostate epithelial cells.

Main Results:

  • Transformed human prostate epithelial cells lacking PTEN require mTORC2 for tumor formation in vivo.
  • Rictor acts as a haploinsufficient gene, where deleting one copy confers protection against prostate cancer in Pten heterozygous mice.
  • Prostate cancer development driven by Pten deletion specifically requires mTORC2, while normal prostate cells do not depend on mTORC2 activity.
  • mTORC2 activity is nonessential for normal prostate epithelial cells.

Conclusions:

  • mTORC2 plays a critical and selective role in the development of PTEN-deficient prostate cancer.
  • The findings highlight mTORC2 as a potential therapeutic target for prostate cancer.
  • Targeting mTORC2 may offer a clinically relevant strategy for treating prostate cancer, particularly in cases with PTEN loss.

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