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TNF-alpha enhances estrogen-induced cell ... ntaining nuclear factor-kappa B


TNF-alpha enhances estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing nuclear factor-kappa B

7350

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 MF, Werbajh S, Cafferata EG, Quaglino A, Coló GP, Nojek IM, Kordon EC, Nahmod VE, Costas MA

Oncogene

2006-03-02 00:00

25

9

1367-77

Animals,Breast Neoplasms,Carcinoma, Ductal, Breast,Cell Proliferation,Chromatin Immunoprecipitation,Cyclin D1,Estrogens,Female,Humans,Mice,NF-kappa B,Receptors, Estrogen,Tumor Cells, Cultured,Tumor Necrosis Factor-alpha,Estrogens,NF-kappa B,Receptors, Estrogen,Tumor Necrosis Factor-alpha,Cyclin D1

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.

Oncogene


0950-9232

10.1038/sj.onc.1209176

1209176

0

False

16331275

Ignacio Nojek
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