The NF-κB transcription factor family members play pivotal roles in several biological and molecular processes. Two pathways of activation of NF-κB family members exist: a classical pathway involving a sequence of events leading to nuclear translocation of p65:p50 heterodimers and a non-canonical pathway involving the partial signal-induced processing of NF-κB2/p100 and the nuclear translocation of p52-containing heterodimers. NF-κB proteins are involved in a variety of lymphoid and epithelial cancers as well as prostate cancer. In this chapter, the role of classical NF-κB is briefly described while the novel role of NF-κB2/p52 in prostate cancer is discussed in detail. Activated STAT3 mediates enhanced processing of p100 leading to higher levels of p52 in prostate cancer. NF-κB2/p52 is overexpressed in prostate cancer, interacts with the androgen receptor in prostate cancer, and enhances ligand-independent growth and survival of prostate cancer cells. In addition, p52 regulates a wide variety of target genes that are involved in metastasis and angiogenesis. Downregulation of endogenous p52 in prostate cancer cells inhibits prostate cancer growth. NF-κB2/p52 is strongly implicated in the progression of castration-resistant prostate cancer, suggesting that targeting this transcription factor may have beneficial effects in therapy of this disease.
|Original language||English (US)|
|Title of host publication||Prostate Cancer|
|Subtitle of host publication||Biochemistry, Molecular Biology and Genetics|
|Publisher||Springer New York|
|Number of pages||17|
|State||Published - Jan 1 2013|
ASJC Scopus subject areas