Abstract
Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate IkB kinase a (IKKa) to accelerate the emergence of castrationresistant tumors. We now demonstrate that infiltrating B lymphocytes and IKKa are also required for androgendependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKKa phosphorylates transcription factor E2F1 on a site that promotes its nuclear translocation, association with the coactivator CBP, and recruitment to critical genomic targets that include Bmi1, a key regulator of normal and cancerous prostate stem cell renewal. The IKKa-BMI1 pathway is also activated in human PCa.
Original language | English (US) |
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Pages (from-to) | 1435-1440 |
Number of pages | 6 |
Journal | Genes and Development |
Volume | 27 |
Issue number | 13 |
DOIs | |
State | Published - Jul 1 2013 |
Externally published | Yes |
Keywords
- B cells
- Prostate
- Regeneration
ASJC Scopus subject areas
- Genetics
- Developmental Biology