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

• Published in: Biomolecules (Basel, Switzerland) Vol. 12; no. 10; p. 1511
• Main Authors: Wise, Helen M, Harris, Adam, Kriplani, Nisha, Schofield, Adam, Caldwell, Helen, Arends, Mark J, Overton, Ian M, Leslie, Nick R
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2022; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; Adenocarcinoma; AKT protein; Analysis; Androgens; Animals; Antibodies; CD44 antigen; Cloning; Development and progression; Gene expression; Identification and classification; Kinases; Lipids; Lymphocytes; Male; Medical prognosis; Metastases; Mice; Nkx3.1 protein; Phenotypes; Phosphatase; Phosphatases; Phosphatidylinositol 3-Kinases - metabolism; Phosphoprotein Phosphatases; Phosphorylation; PI 3-Kinase; Properties; Prostate - metabolism; Prostate cancer; Prostatic intraepithelial neoplasia; Prostatic Neoplasms - metabolism; Protein expression; Protein phosphatase; Proteins; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; PTEN; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN protein; Tumor necrosis factor; Tumors; tumour suppressor; United Kingdom; United Kingdom > UK; Germany; PTEN; prostate cancer; phosphatase; PI 3-Kinase; tumour suppressor
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom12101511

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 or 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 and ). 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.