Bmi-1 is a crucial regulator of prostate stem cell self-renewal and malignant transformation
- PMID: 21112563
- PMCID: PMC3019762
- DOI: 10.1016/j.stem.2010.11.013
Bmi-1 is a crucial regulator of prostate stem cell self-renewal and malignant transformation
Abstract
The Polycomb group transcriptional repressor Bmi-1 is often upregulated in prostate cancer, but its functional roles in prostate stem cell maintenance and prostate cancer are unclear. Loss- and gain-of-function analysis in a prostate sphere assay indicates that Bmi-1 expression is required for self-renewal activity and maintenance of p63(+) stem cells. Loss of Bmi-1 blocks the self-renewal activity induced by heightened β-catenin signaling, suggesting that Bmi-1 is required for full activity of another self-renewal pathway. In vivo, Bmi-1 expression is necessary for normal prostate tubule regeneration. Altered self-renewal and proliferation through Bmi-1 modulation diminishes the susceptibility of prostate cells to transformation. In an in vivo prostate regeneration system, Bmi-1 inhibition protects prostate cells from FGF10-driven hyperplasia and slows the growth of aggressive Pten-deletion-induced prostate cancer. We conclude that Bmi-1 is a crucial regulator of self-renewal in adult prostate cells and plays important roles in prostate cancer initiation and progression.
Copyright © 2010 Elsevier Inc. All rights reserved.
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Comment in
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An old player on a new playground: bmi-1 as a regulator of prostate stem cells.Cell Stem Cell. 2010 Dec 3;7(6):639-40. doi: 10.1016/j.stem.2010.11.019. Cell Stem Cell. 2010. PMID: 21112554 No abstract available.
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Bmi-1, stem cells and prostate carcinogenesis.Asian J Androl. 2011 May;13(3):353-4. doi: 10.1038/aja.2011.7. Epub 2011 Feb 21. Asian J Androl. 2011. PMID: 21336300 Free PMC article. No abstract available.
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References
-
- Asselin-Labat ML, Vaillant F, Shackleton M, Bouras T, Lindeman GJ, Visvader JE. Delineating the epithelial hierarchy in the mouse mammary gland. Cold Spring Harb Symp Quant Biol. 2008;73:469–478. - PubMed
-
- Bisson I, Prowse DM. WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics. Cell Res. 2009;19:683–697. - PubMed
-
- Carson CC., 3rd Carcinoma of the prostate: overview of the most common malignancy in men. N C Med J. 2006;67:122–127. - PubMed
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