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PTEN: a new guardian of the genome

Oncogene volume 27, pages 5443–5453 (2008)Cite this article

Abstract

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor is a phosphatase that antagonizes the phosphoinositol-3-kinase/AKT signaling pathway and suppresses cell survival as well as cell proliferation. PTEN is the second most frequently mutated gene in human cancer after p53. Germline mutations of PTEN have been found in cancer susceptibility syndromes, such as Cowden syndrome, in which over 80% of patients have mutations of PTEN. Homozygous deletion of Pten causes embryonic lethality, suggesting that PTEN is essential for embryonic development. Mice heterozygous for Pten develop spontaneous tumors in a variety of organs comparable with the spectrum of its mutations in human cancer. The mechanisms of PTEN functions in tumor suppression are currently under intense investigation. Recent studies demonstrate that PTEN plays an essential role in the maintenance of chromosomal stability and that loss of PTEN leads to massive alterations of chromosomes. The tumor suppressor p53 is known as a guardian of the genome that mediates the cellular response to environmental stress, leading to cell cycle arrest or cell death. Through completely different mechanisms, PTEN also protects the genome from instability. Thus, we propose that PTEN is a new guardian of the genome. In this review, we will discuss new discoveries on the role of PTEN in tumor suppression and explore mechanisms by which PTEN maintains genomic stability.

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Acknowledgements

We are grateful to Drs C Walsh and HB Lieberman for their critical comments on the manuscript. This work was supported by a grant from the National Institutes of Health (R01 CA102447 to YY).

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  1. Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Y Yin & W H Shen

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  1. Y Yin
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  2. W H Shen
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Correspondence to Y Yin.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Yin, Y., Shen, W. PTEN: a new guardian of the genome. Oncogene 27, 5443–5453 (2008). https://doi.org/10.1038/onc.2008.241

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