Abstract
PTEN is one of the most commonly deleted/mutated tumor suppressor genes in human prostate cancer. As a lipid phosphatase and negative regulator of the PI3K/AKT/mTOR pathway, PTEN controls a number of cellular processes, including survival, growth, proliferation, metabolism, migration, and cellular architecture. Over the past 15 years since its discovery, a number of mechanisms governing PTEN expression and function, including transcriptional and post-transcriptional regulation, post-translational modifications, and protein–protein interactions, have been shown to be altered in human prostate cancer. The functions of PTEN within the cell have been expanded to include phosphatase-independent roles and functions within the nucleus. The generation of genetically engineered mouse models (GEMs) with deletion of Pten has further revealed that varying degrees of Pten loss in combination with other genetic alterations are able to recapitulate all spectrums of human prostate cancer, from tumor initiation to metastasis. With new methods of genomic and transcriptional analysis of human prostate cancer specimens, PTEN loss can potentially be used as a diagnostic and prognostic biomarker for prostate cancer, as well as predict patient responses to emerging PI3K/AKT/mTOR inhibitors. Finally, deeper insight into communication between the PI3K/AKT/mTOR and Ras/MAPK signaling pathways has led to the creation of metastatic murine prostate cancer models that develop lethal metastases, while new understanding of a feedback loop between PTEN and androgen receptor (AR) controlled pathways has unveiled a new mechanism for the development of castration-resistant prostate cancer (CRPC). Our expanded knowledge of PTEN and its role in prostate cancer initiation and Âprogression will inform the rational design of novel therapeutics that target PTEN-controlled pathways alone or in combination with other related pathways for the treatment of metastatic and castration-resistant prostate cancer.
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Ruscetti, M.A., Wu, H. (2013). PTEN in Prostate Cancer. In: Tindall, D. (eds) Prostate Cancer. Protein Reviews, vol 16. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6828-8_4
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