TNF-alpha enhances estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing nuclear factor-kappa B.
Breast tumors are usually classified according to their response to estrogens as hormone-dependent or -independent. In this work, we investigated the role of the proinflammatory cytokine TNF-alpha on the estrogen-receptor-positive T47D breast ductal tumor cells. We have found that TNF-alpha exerts a mitogenic effect, inducing cyclin D1 expression and activation of the transcription factor NF-kappaB. Importantly, activation of NF-kappaB was required for estrogen-induced proliferation and cyclin D1 expression. TNF-alpha enhanced the estrogen response by increasing the levels and availability of NF-kappaB. Chromatin immunoprecipitation analysis suggested that the action of estrogens is mediated by a protein complex that contains the activated estrogen receptor, the nuclear receptor coactivator RAC3 and a member of the NF-kappaB family. Finally, our results demonstrate that activation of this transcription factor could be one of the key signals for estrogen-mediated response.
Rubio
M F
MF
Laboratorio de Biología Molecular y Apoptosis, Departamento de Sustancias Vasoactivas, Instituto de Investigaciones Médicas Alfredo Lanari, IDIM-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Werbajh
S
S
Cafferata
E G A
EG
Quaglino
A
A
Coló
G P
GP
Nojek
I M
IM
Kordon
E C
EC
Nahmod
V E
VE
Costas
M A
MA
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D019938:Cyclin D1 / Q000096:biosynthesis; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004967:Estrogens; D016328:NF-kappa B; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; D019938:Cyclin D1