Journal article
An IKKα–E2F1–BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence
Genes & development, Vol.27(13), pp.1435-1440
07/01/2013
DOI: 10.1101/gad.220202.113
PMCID: PMC3713424
PMID: 23796898
Abstract
Androgen-deprived prostate cancer (PCa) is infiltrated by B cells that produce cytokines to activate IκB kinase α (IKKα), which accelerates the emergence of castration-resistant tumors. Ammirante et al. find that infiltrating B cells and IKKα are required for prostate regeneration. In epithelial progenitors and PCa cells, IKKα phosphorylates E2F1, leading to its nuclear translocation, association with the coactivator CBP, and recruitment to critical genomic targets, including a regulator of prostate stem cell renewal, Bmi1. They find that the IKKα-BMI1 pathway is also activated in human PCa.
Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate IκB kinase α (IKKα) to accelerate the emergence of castration-resistant tumors. We now demonstrate that infiltrating B lymphocytes and IKKα are also required for androgen-dependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKKα 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 IKKα–BMI1 pathway is also activated in human PCa.
Details
- Title: Subtitle
- An IKKα–E2F1–BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence
- Creators
- Massimo Ammirante - Laboratory of Gene Regulation and Signal Transduction, Department of PharmacologyAli I Kuraishy - Laboratory of Gene Regulation and Signal Transduction, Department of PharmacologyShabnam Shalapour - Laboratory of Gene Regulation and Signal Transduction, Department of PharmacologyAmy Strasner - Laboratory of Gene Regulation and Signal Transduction, Department of PharmacologyClaudia Ramirez-Sanchez - Laboratory of Gene Regulation and Signal Transduction, Department of PharmacologyWeizhou Zhang - Laboratory of Gene Regulation and Signal Transduction, Department of PharmacologyAhmed Shabaik - Department of Pathology, School of Medicine, University of California at San Diego, La Jolla, California 92093, USAMichael Karin - Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology
- Resource Type
- Journal article
- Publication Details
- Genes & development, Vol.27(13), pp.1435-1440
- Publisher
- Cold Spring Harbor Laboratory Press
- DOI
- 10.1101/gad.220202.113
- PMID
- 23796898
- PMCID
- PMC3713424
- ISSN
- 0890-9369
- eISSN
- 1549-5477
- Language
- English
- Date published
- 07/01/2013
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984083265602771
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