Tumor Necrosis Factor-α-induced Apoptosis in Prostate Cancer Cells through Inhibition of Nuclear Factor-κB by an IκBα “Super-Repressor”

摘要: Prostate cancer patients experiencing a relapse in disease often express high serum tumor necrosis factor-alpha (TNF-alpha) levels. Many androgen-insensitive prostate cells are TNF-alpha insensitive because of the expression antiapoptotic genes as part nuclear factor-kappaB (NF-kappaB) family transcription factors. NF-kappaB stimulates gene when expressed nucleus; however, resting cells, this import is prevented by association with cytoplasmic inhibitor IkappaBalpha. This retention uncoupled many extracellular signals including low levels TNF-alpha. During normal cell activation, translocation preceded phosphorylation and degradation When blocked, IkappaBalpha remains intact, thereby blocking to nucleus subsequent activation that cause insensitivity. We tested whether "super-repressor" activity could be transfected into make them sensitive. PC-3 LNCaP were stimulated (10 ng/ml) for 24 h presence or absence (p6R-IkappaB(S32A + S36A)). was measured electrophoretic mobility shift assay steady state protein Western blot. Secretory IL-6 mRNA ELISA. p6R-IkappaB(S32A S36A) blocked stimulation cells. It also subsequently decreased production conclude these data demonstrate inhibition selectively sensitizes previously