[PDF][PDF] Bmi-1 is a crucial regulator of prostate stem cell self-renewal and malignant transformation

RU Lukacs, S Memarzadeh, H Wu, ON Witte - Cell stem cell, 2010 - cell.com
RU Lukacs, S Memarzadeh, H Wu, ON Witte
Cell stem cell, 2010cell.com
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 …
Summary
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.
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