World Journal of Urology

, Volume 30, Issue 3, pp 303–310 | Cite as

NF-κB signaling in prostate cancer: A promising therapeutic target?

  • Garima Jain
  • Marcus V. Cronauer
  • Mark Schrader
  • Peter Möller
  • Ralf B. Marienfeld
Topic paper

Abstract

Prostate carcinoma (PCa) displays a wide variety of genetic alterations, versatile expression profiles as well as cell surface markers. Despite this heterogeneity, a common treatment for advanced PCa is androgen deprivation therapy (ADT). ADT targets the androgen receptor—a member of the nuclear receptor superfamily—which is required for development and function of the prostate and critical for PCa growth and survival. After an initial regression of the tumor during ADT, a large fraction of tumors progress to so-called castration-resistant prostate carcinoma (CRPca) which is highly resistant toward chemotherapy. The ensuing high mortality rates illustrate the importance of novel therapeutic targets for CRPCa. The transcription factor NF-κB was recently proposed as such a potential target for therapeutic intervention in CRPCa. Although NF-κB is essential for the regulation of innate and adaptive immunity recent data suggest a role of NF-κB in cancer initiation and progression. However, the exact function of NF-κB signaling in PCa is still a matter of debate. Here, we review known roles of NF-κB signaling in PCa and emphasize the crosstalk of NF-κB and androgen receptor signaling. Finally, we discuss potential therapeutic relevance of blocking NF-κB in PCa.

Keywords

NF-κB Prostate carcinoma Androgen receptor Castration 

Abbreviations

ADT

Androgen deprivation therapy

AR

Androgen receptor

ARE

Androgen receptor element

BAFF

B-cell activating factor

CRPCa

Castration-resistant PCa

DHT

Dihydrotestosterone

DNMT1

DNA methyl transferase I

EMT

Epithelial-to-Mesemchymal-Transition

HDAC

Histone deacetylase

HSP

Heat shock protein

IκB

Inhibitor of NF-κB

IKK

IκB kinase

NIK

NF-κB inducing kinase

PCa

Prostate carcinoma

SHBG

Steroid hormone binding globuline

STAT

Signal transducer and activator of transcription

TGFβ

Transforming Growth Factor β

TNFα

Tumor necrosis factor alpha

TRADD

TNFR1-associated death domain protein

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Garima Jain
    • 1
  • Marcus V. Cronauer
    • 2
  • Mark Schrader
    • 2
  • Peter Möller
    • 1
  • Ralf B. Marienfeld
    • 1
  1. 1.Institute of PathologyUniversity of UlmUlmGermany
  2. 2.Department of UrologyUniversity of UlmUlmGermany

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