Reduced tumor necrosis factor receptor-associated death domain expression is associated with prostate cancer progression.
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.
Wang
Diping
D
Department of Urology Research/Biochemistry, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Montgomery
R Bruce
RB
Schmidt
Lucy J
LJ
Mostaghel
Elahe A
EA
Huang
Haojie
H
Nelson
Peter S
PS
Tindall
Donald J
DJ
D000368:Aged; D000369:Aged, 80 and over; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000172:deficiency; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D053199:TNF Receptor-Associated Death Domain Protein / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D059002:Androgen Receptor Antagonists; D000728:Androgens; D016328:NF-kappa B; D011944:Receptors, Androgen; D053199:TNF Receptor-Associated Death Domain Protein; D014409:Tumor Necrosis Factor-alpha