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Pten Deletion Leads to the Expansion of a Prostatic Stem/Progenitor Cell Subpopulation and Tumor Initiation

PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a potent tumor suppressor gene frequently mutated in human prostate cancers. Deletion of Pten in a murine model of prostate cancer recapitulates the disease progression seen in humans. Using defined cell lineage markers, we demonstrat...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-01, Vol.103 (5), p.1480-1485
Main Authors: Wang, Shunyou, Garcia, Alejandro J., Wu, Michelle, Lawson, Devon A., Witte, Owen N., Wu, Hong
Format: Article
Language:English
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Summary:PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a potent tumor suppressor gene frequently mutated in human prostate cancers. Deletion of Pten in a murine model of prostate cancer recapitulates the disease progression seen in humans. Using defined cell lineage markers, we demonstrate that PTEN negatively regulates p63-positive prostatic basal cell proliferation without blocking differentiation. Concomitant with basal cell proliferation is the expansion of a prostate stem/progenitorlike subpopulation as evidenced by the progressive increase of stem cell antigen-1 (Sca-1)-and BCL-2-positive cells. This observation provides strong evidence that basal cell proliferation can be an initiating event for precancerous lesions. Sca-1⁺ and BCL-2⁺ progenitors may serve as cancer-initiating cells in this model.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0510652103