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

Oncogene volume 25, pages 1367–1377 (2006)Cite this article

Abstract

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-α on the estrogen-receptor-positive T47D breast ductal tumor cells. We have found that TNF-α exerts a mitogenic effect, inducing cyclin D1 expression and activation of the transcription factor NF-κB. Importantly, activation of NF-κB was required for estrogen-induced proliferation and cyclin D1 expression. TNF-α enhanced the estrogen response by increasing the levels and availability of NF-κB. 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-κB family. Finally, our results demonstrate that activation of this transcription factor could be one of the key signals for estrogen-mediated response.

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Abbreviations

TRADD:

TNF receptor-associated death domain

FADD:

FAS-associated death domain

ER:

estrogen receptor

SZ:

sulfasalazine

17E:

17-β-estradiol

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Acknowledgements

This work has been supported by grants from the Argentine National Research Council (CONICET), Agencia Nacional de Promoción Científica y Tecnológica and Fundación Antorchas, Argentina. We thank Dr Claudio Pereira, Dr Estela Medrano, Dr Christiane D Pasqualini and Dr Omar Coso for comments about the manuscript. We also thank Dr Nancy Hynes for kindly providing us the HC11 mouse mammary cell line, and Dr Fernando Pitossi, who has provided the adenoviral vector used in this work.

Author information

Author notes

  1. M F Rubio and S Werbajh: These authors contributed equally to this work.

  2. E C Kordon and M A Costas: Member of Research Career, CONICET (National Research Council).

Authors and Affiliations

  1. Departamento de Sustancias Vasoactivas, Laboratorio de Biología Molecular y Apoptosis, Instituto de Investigaciones Médicas Alfredo Lanari, IDIM-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    M F Rubio, S Werbajh, G P Coló, I M Nojek, V E Nahmod & M A Costas

  2. Centro Nacional de Genética Médica–ANLIS–Carlos G Malbrán and Leloir Institute Fundation (FIL), Buenos Aires, Argentina

    E G A Cafferata

  3. ILEX-CONICET, División Medicina, Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina

    A Quaglino & E C Kordon

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  1. M F Rubio
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  2. S Werbajh
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Correspondence to M A Costas.

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Rubio, M., Werbajh, S., Cafferata, E. et al. TNF-α enhances estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing nuclear factor-kappa B. Oncogene 25, 1367–1377 (2006). https://doi.org/10.1038/sj.onc.1209176

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