NF-κB regulates androgen receptor expression and prostate cancer growth Journal Article

Authors: Zhang, L.; Altuwaijri, S.; Deng, F.; Chen, L.; Lal, P.; Bhanot, U. K.; Korets, R.; Wenske, S.; Lilja, H. G.; Chang, C.; Scher, H. I.; Gerald, W. L.
Article Title: NF-κB regulates androgen receptor expression and prostate cancer growth
Abstract: Prostate cancers that progress during androgen-deprivation therapy often overexpress the androgen receptor (AR) and depend on AR signaling for growth. In most cases, increased AR expression occurs without gene amplification and may be due to altered transcriptional regulation. The transcription factor nuclear factor (NF)-κB, which is implicated in tumorigenesis, functions as an important downstream substrate of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, AKT, and protein kinase C and plays a role in other cancer-associated signaling pathways. NF-κB is an important determinant of prostate cancer clinical biology, and therefore we investigated its role in the regulation of AR expression. We found that NF-κB expression in prostate cancer cells significantly increased AR mRNA and protein levels, AR transactivation activity, serum prostate-specific antigen levels, and cell proliferation. NF-κB inhibitors decrease AR expression levels, prostate-specific antigen secretion, and proliferation of prostate cancer cells in vitro. Furthermore, inhibitors of NF-κB demonstrated anti-tumor activity in androgen deprivation-resistant prostate cancer xenografts. In addition, levels of both NF-κB and AR were strongly correlated in human prostate cancer. Our data suggest that NF-κB can regulate AR expression in prostate cancer and that NF-κB inhibitors may have therapeutic potential. Copyright © American Society for Investigative Pathology.
Keywords: controlled study; human tissue; protein expression; human cell; promoter region; genetics; cancer growth; nonhuman; antineoplastic agents; antineoplastic agent; cell proliferation; prostate specific antigen; mouse; animal; metabolism; animals; mice; animal tissue; animal experiment; animal model; protein; immunoglobulin enhancer binding protein; transcription factor rela; antineoplastic activity; in vitro study; tumor xenograft; drug screening; pathology; xenograft model antitumor assays; cell line, tumor; cancer resistance; prostate cancer; prostatic neoplasms; gene expression regulation; gene expression regulation, neoplastic; drug antagonism; nude mouse; mice, nude; messenger rna; promoter regions, genetic; nucleotide sequence; cancer cell; prostate tumor; nf-kappa b; tumor cell line; transactivation; androgen receptor; receptors, androgen; sesquiterpenes; parthenolide; ar protein, human; sesquiterpene
Journal Title: American Journal of Pathology
Volume: 175
Issue: 2
ISSN: 0002-9440
Publisher: Elsevier Science, Inc.  
Date Published: 2009-08-01
Start Page: 489
End Page: 499
Language: English
DOI: 10.2353/ajpath.2009.080727
PUBMED: 19628766
PROVIDER: scopus
PMCID: PMC2716950
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 30 November 2010" - "CODEN: AJPAA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Ruslan Korets
    9 Korets
  2. William L Gerald
    375 Gerald
  3. Sven Wenske
    5 Wenske
  4. Hans Gosta Lilja
    300 Lilja
  5. Liying Zhang
    108 Zhang
  6. Lishi Chen
    18 Chen
  7. Umeshkumar Kapaldev Bhanot
    41 Bhanot
  8. Howard Scher
    976 Scher