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

Helen M. Wise, Adam Harris, Nisha Kriplani, Adam Schofield, Helen Caldwell, Mark J. Arends, Ian Michael Overton, Nicholas R. Leslie

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Loss PTEN function is one of the most common events driving aggressive prostate cancers and biochemically, PTEN is a lipid phosphatase which opposes the activation of the oncogenic PI3K-AKT signalling network. However, PTEN also has additional potential mechanisms of action, including protein phosphatase activity. Using a mutant enzyme, PTEN Y138L, which selectively lacks protein phosphatase activity, we characterised genetically modified mice lacking either the full function of PTEN in the prostate gland or only lacking protein phosphatase activity. The phenotypes of mice carrying a single allele of either wild-type Pten or PtenY138L in the prostate were similar, with common prostatic intraepithelial neoplasia (PIN) and similar gene expression profiles. However, the latter group, lacking PTEN protein phosphatase activity additionally showed lymphocyte infiltration around PIN and an increased immune cell gene expression signature. Prostate adenocarcinoma, elevated proliferation and AKT activation were only frequently observed when PTEN was fully deleted. We also identify a common gene expression signature of PTEN loss conserved in other studies (including Nkx3.1, Tnf and Cd44). We provide further insight into tumour development in the prostate driven by loss of PTEN function and show that PTEN protein phosphatase activity is not required for tumour suppression.
Original languageEnglish
Article number1511
Issue number10
Publication statusPublished - 19 Oct 2022


  • phosphatase
  • PI 3-Kinase
  • prostate cancer
  • PTEN
  • tumour suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry


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