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PTEN Protein Phosphatase Activity Is Not Required for Tumour Suppression in the Mouse Prostate

Helen M Wise1, Adam Harris2, Nisha Kriplani1

  • 1Institute of Biological Chemistry, Biophysics and Bioengineering, Riccarton Campus, Heriot Watt University, Nasmyth Building, Edinburgh EH14 4AS, UK.

Biomolecules
|October 27, 2022
PubMed

Insights

Loss of PTEN function drives aggressive prostate cancer. However, PTEN

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Phosphatase and tensin homolog (PTEN) is a tumor suppressor.
  • PTEN loss is common in aggressive prostate cancers.
  • PTEN has both lipid and protein phosphatase activities.

Purpose of the Study:

  • To investigate the role of PTEN's protein phosphatase activity in prostate cancer.
  • To differentiate the functions of PTEN's lipid and protein phosphatase activities in vivo.
  • To understand the mechanisms of PTEN loss-driven prostate tumorigenesis.

Main Methods:

  • Genetically modified mice lacking PTEN function or only protein phosphatase activity.
  • Analysis of prostatic intraepithelial neoplasia (PIN) and gene expression profiles.
  • Comparison of phenotypes between wild-type PTEN and PTEN Y138L mutant models.

Main Results:

  • PTEN protein phosphatase activity is not required for tumor suppression.
  • Loss of PTEN protein phosphatase activity led to lymphocyte infiltration and immune gene signature.
  • Prostate adenocarcinoma, proliferation, and AKT activation were observed only upon complete PTEN deletion.
  • A conserved gene expression signature of PTEN loss was identified.

Conclusions:

  • PTEN's protein phosphatase activity is dispensable for its tumor-suppressive function in the prostate.
  • PTEN's lipid phosphatase activity is critical for preventing prostate adenocarcinoma.
  • PTEN loss triggers distinct molecular events impacting tumor microenvironment and progression.
Keywords:
PI 3-KinasePTENphosphataseprostate cancertumour suppressor

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