Reduced tumor necrosis factor receptor-associated death domain expression is associated with prostate cancer progression

Diping Wang, R. Bruce Montgomery, Lucy J. Schmidt, Elahe A. Mostaghe, Haojie Huang, Peter S. Nelson, Donald J. Tindall

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

By using LNCaP and its derivative cell lines, we first observed an association between tumor necrosis factor-α (TNF-α) resistance and hormone independence. Moreover, we found that the expression of tumor necrosis factor receptor-associated death domain (TRADD) was reduced in androgen deprivation-independent cells compared with that in androgen deprivation-dependent cells. TRADD is a crucial transducer for TNF-α-induced nuclear factor-κB (NF-κB) activation. Knocking down TRADD expression in LNCaP cells impaired TNF-α-induced NF-κB activation and androgen receptor repression, whereas overexpression of TRADD in C4-2B cells restored their sensitivity to TNF-α. Finally, we found that androgen deprivation reduces TRADD expression in vitro and in vivo, suggesting that androgen deprivation therapy may promote the development of TNF-α resistance by reducing TRADD expression during prostate cancer progression.

Original languageEnglish (US)
Pages (from-to)9448-9456
Number of pages9
JournalCancer research
Volume69
Issue number24
DOIs
StatePublished - Dec 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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