TNF-[alpha] enhances estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing nuclear factor-kappa B.
Rubio, M F 1,5; Werbajh, S 1,5; Cafferata, E GA 2; Quaglino, A 3; Colo, G P 1; Nojek, I M 1; Kordon, E C 3,4; Nahmod, V E 1; Costas, M A 1,4
[Article] Oncogene. 25(9):1367-1377, March 2, 2006.

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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-[kappa]B. Importantly, activation of NF-[kappa]B was required for estrogen-induced proliferation and cyclin D1 expression. TNF-[alpha] enhanced the estrogen response by increasing the levels and availability of NF-[kappa]B. 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-[kappa]B 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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