TNF-? enhances Estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing

RUBIO M F; WERBAJH S E; CAFFERATA E,; COLO, G.; NOJEK, I.; NAHMOD, V. E.; MONICA ALEJANDRA COSTAS

Oncogene

Año: 2006 vol. 25 p. 1367 - 1377

0950-9232

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 pro-inflammatory cytokine TNF-a on the estrogen receptor positive T47D breast ductal tumor cells. We have found that TNF-a exerts a mitogenic effect, inducing cyclin D1 expression and activation of the transcription factor NF-kB. Importantly, activation of NF-kB was required for estrogen-induced proliferation and Cyclin D1 expression. TNF-a_ enhanced the estrogen response by increasing the levels and availability of NF-kB. Chromatin immunoprecipitation analysis suggested that, the action of estrogens is mediated by a protein complex that contain the activated estrogen receptor, the nuclear receptor coactivator RAC3 and a member of the NF-kB family. Finally, our results demonstrate that activation of this transcription factor could be one of the key signals for estrogen-mediated response.