NF-κB suppression provokes the sensitization of hormone-resistant breast cancer cells to estrogen apoptosis
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The progression of breast cancer cells to estrogen-independent growth may be accompanied with the paradoxical cell sensitization to estrogen apoptotic action; however, the mechanism of this phenomenon is still unclear. In the present study, we have shown that the sensitization of hormone-resistant breast cancer cells to estrogen apoptotic action is accompanied with the gradual NF-κB suppression. Using the chemical inhibitors of NF-κB as well as the dominant-negative NF-κB constructs, we have proved the sufficiency of NF-κB inhibition for the sensitization of the resistant cells to estrogen apoptosis. Estradiol treatment results in the additional suppression of NF-κB, demonstrating the possible NF-κB involvement in the regulation of cell response to estrogens. Totally, the results presented suggest that the constitutive NF-κB suppression in the estrogen-independent cells may be considered as one of the factors resulting in a imbalance between pro- and anti-apoptotic pathways and enhancement in estrogen apoptotic action in the cells.
KeywordsBreast cancer NF-κB Apoptosis Estrogen MCF-7
This work was supported in part by the Russian Foundation for Basic Research (www.rfbr.ru), grant 07-04-00573. We thank Olga Burova (Russian N.N. Blokhin Cancer Research Centre, Moscow, Russia) for assistance in FACS analysis.
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