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

Publication Type:

Journal Article

Source:

Cancer research, Volume 69, Issue 24, p.9448-56 (2009)

Keywords:

2009, Aged, Aged, 80 and over, Androgen Receptor Antagonists, androgens, Cell Line, Tumor, Cell Survival, Center-Authored Paper, Clinical Research Division, DISEASE PROGRESSION, Genomics Core Facility, Human Biology Division, Humans, Male, Middle Aged, Neoplasms, Hormone-Dependent, NF-kappa B, Prostatic Neoplasms, Receptors, Androgen, Shared Resources, TNF Receptor-Associated Death Domain Protein, Transfection, Tumor Necrosis Factor-alpha

Abstract:

By using LNCaP and its derivative cell lines, we first observed an association between tumor necrosis factor-alpha (TNF-alpha) 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-alpha-induced nuclear factor-kappaB (NF-kappaB) activation. Knocking down TRADD expression in LNCaP cells impaired TNF-alpha-induced NF-kappaB activation and androgen receptor repression, whereas overexpression of TRADD in C4-2B cells restored their sensitivity to TNF-alpha. 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-alpha resistance by reducing TRADD expression during prostate cancer progression.