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

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.

SUBMITTER: Wang D 

PROVIDER: S-EPMC2795008 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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

Wang Diping D   Montgomery R Bruce RB   Schmidt Lucy J LJ   Mostaghel Elahe A EA   Huang Haojie H   Nelson Peter S PS   Tindall Donald J DJ  

Cancer research 20091201 24

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  ...[more]

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