RelB enhances prostate cancer growth: Implications for the role of the nuclear factor-κb alternative pathway in tumorigenicity

Yong Xu, Sajni Josson, Fang Fang, Terry D. Oberley, Daret K.St Clair, X. Steven Wan, Yulan Sun, Vasudevan Bakthavatchalu, Anantharaman Muthuswamy, William H.St Clair

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

The nuclear faetor-κB (NP-κB) classic pathway is thought to be critical for tumorigenesis, but little is known about the role of the NF-κB alternative pathway in cancer development. Recently, high constitutive nuclear levels of RelB have been observed in human prostate cancer specimens with high Gleason scores. Here, we used four complementary approaches to test whether RelB contributes to tumorigenicity of prostate cancer. Inhibiting RelB in aggressive androgenindependent PC-3 cells by stable or conditional expression of a dominant-negative p100 mutant significantly reduced the incidence and growth rate of tumors. The decrease in tumorigenicity coincided with a reduction in the NF-κB target interleukin-8 (IL-8). Consistently, down-regulation of RelB by small interfering RNA targeting also reduced tumor growth and decreased levels of IL-8. Conversely, stable expression of RelB in androgen-responsive LNCaP tumors increased the circulating IL-8 levels. Taken together, these results reveal a tumor-supportive role of RelB, implicate the NF-κB alternative pathway as a potential target for preventing prostate cancer, and suggest the use of IL-8 as a marker for prostate cancer prognosis.

Original languageEnglish
Pages (from-to)3267-3271
Number of pages5
JournalCancer Research
Volume69
Issue number8
DOIs
StatePublished - Apr 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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