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 language | English (US) |
---|---|
Pages (from-to) | 9448-9456 |
Number of pages | 9 |
Journal | Cancer research |
Volume | 69 |
Issue number | 24 |
DOIs | |
State | Published - Dec 15 2009 |
ASJC Scopus subject areas
- Oncology
- Cancer Research