NF-kappaB activation in human prostate cancer: important mediator or epiphenomenon?

J Cell Biochem. 2004 Jan 1;91(1):100-17. doi: 10.1002/jcb.10729.


The NF-kappaB family of transcription factors has been shown to be constitutively activated in various human malignancies, including leukemias, lymphomas, and a number of solid tumors. NF-kappaB is hypothesized to contribute to development and/or progression of malignancy by regulating the expression of genes involved in cell growth and proliferation, anti-apoptosis, angiogenesis, and metastasis. Prostate cancer cells have been reported to have constitutive NF-kappaB activity due to increased activity of the IkappaB kinase complex. Furthermore, an inverse correlation between androgen receptor (AR) status and NF-kappaB activity was observed in prostate cancer cell lines. NF-kappaB may promote cell growth and proliferation in prostate cancer cells by regulating expression of genes such as c-myc, cyclin D1, and IL-6. NF-kappaB may also inhibit apoptosis in prostate cancer cells through activation of expression of anti-apoptotic genes, such as Bcl-2, although pro-apoptotic activity of NF-kappaB has also been reported. NF-kappaB-mediated expression of genes involved in angiogenesis (IL-8, VEGF), and invasion and metastasis (MMP9, uPA, uPA receptor) may further contribute to the progression of prostate cancer. Constitutive NF-kappaB activity has also been demonstrated in primary prostate cancer tissue samples and suggested to have prognostic importance for a subset of primary tumors. The limited number of samples analyzed in those studies and the relative lack of NF-kappaB target genes identified in RNA expression microarray analyses of prostate cancer cells suggest that further studies will be required in order to determine if NF-kappaB actually plays a role in human prostate cancer development, and/or progression, and to characterize its potential as a therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Cell Division / physiology*
  • Cyclin D1 / metabolism
  • Gene Expression Regulation, Neoplastic / physiology*
  • Genes, myc / physiology
  • Humans
  • Male
  • Metalloendopeptidases / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Receptors, Androgen / metabolism*


  • NF-kappa B
  • Receptors, Androgen
  • Cyclin D1
  • Metalloendopeptidases