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Updated: May 20, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

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Published on: July 17, 2019

B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer

Jingqiang Wang1, Takashi Kobayashi, Nicolas Floc'h

  • 1Department of Urology and Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10031, USA.

Cancer Research
|July 28, 2012
PubMed

Insights

Targeting PI3K-Akt-mTOR and MAPK pathways in prostate cancer may offer a new therapeutic strategy. Combined inhibition of these pathways reduces c-Myc, tumor growth, and metastasis in a novel mouse model.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate tumors with poor prognosis often show deregulation of PI3K → Akt → mTOR and mitogen-activated protein kinase (MAPK) signaling pathways.
  • PTEN loss and BRAF(V600E) oncogene activation are key drivers in various cancers.

Purpose of the Study:

  • To develop a novel genetically engineered mouse model for prostate cancer incorporating simultaneous activation of PI3K-Akt-mTOR and MAPK pathways.
  • To investigate the cooperative effects of these activated pathways on tumor progression and metastasis.
  • To evaluate the therapeutic potential of targeting these pathways in prostate cancer.

Main Methods:

  • Generation of a tissue-specific, inducible mouse model with PTEN disruption and BRAF(V600E) expression.
  • Analysis of tumor development, castration resistance, senescence bypass, and metastatic dissemination.
  • Assessment of c-Myc upregulation and the impact of rapamycin and PD0325901 treatment on signaling pathways and tumor burden.

Main Results:

  • The engineered mice developed lethal, castration-resistant prostate tumors with significant metastatic potential (30% incidence).
  • Cooperative activation of PI3K-Akt-mTOR and MAPK pathways led to c-Myc upregulation.
  • Combined inhibition of these pathways with rapamycin and PD0325901 reduced c-Myc levels, tumor growth, and metastatic burden.

Conclusions:

  • The developed mouse model recapitulates aggressive, metastatic prostate cancer driven by PI3K-Akt-mTOR and MAPK pathway activation.
  • Combined targeting of these pathways offers a promising therapeutic strategy to inhibit c-Myc and control prostate cancer progression and metastasis.

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