17 beta-estradiol inhibits tumor necrosis factor-alpha-induced nuclear factor-kappa B activation by increasing nuclear factor-kappa B p105 level in MCF-7 breast cancer cells.
Tumor necrosis factor-alpha (TNF-alpha) exerts many cytological effects on a wide range of cells. TNF-alpha can activate nuclear factor-kappa B (NF-kappa B). Activation of NF-kappa B by TNF-alpha mediates many functions of TNF-alpha. The NF-kappa B inhibitor, I kappa B alpha, negatively regulates the activity of NF-kappa B. In MCF-7 cells (an estrogen and TNF-alpha receptor positive cell line), treatment with 17 beta-estradiol (E(2)) inhibited TNF-alpha-induced NF-kappa B DNA binding activity in the gel retardation assays. But, the level of the I kappa B alpha and the TNF-alpha receptor, TNF-R1, were not obviously affected. The NF-kappa B precursor, NF-kappa B p105, has been shown to be associated with NF-kappa B in the cytoplasm and efficiently blocks its nuclear translocation and activation. Treatment of MCF-7 cells with E(2) increased the level of NF-kappa B p105 protein. The anti-estrogen, 4OH-tamoxifen, treatment inhibited E(2)-induced NF-kappa B p105 expression. Our findings indicate that NF-kappa B p105 plays a role in modulating the functions of TNF-alpha in the estrogen receptor positive breast cancer cells.
Hsu
S M
SM
Department of Pathology, College of Medicine, National Taiwan University, Republic of China.
Chen
Y C
YC
Jiang
M C
MC
D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D015703:Antigens, CD; D017931:DNA Primers; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol