[The nuclear factor kappa B activation: the key step of cell proliferation in estrogen receptor-negative breast cancer cells].

Objective To investigate the way of nuclear factor kappa B(NF-κB) activation and the mechanism of NF-κB-promoted proliferation in estrogen receptor(ER)-negative breast cancer cells. Methods The protein of IκB kinase α(IKKα) was measured by Western blot and the influence on cell-cycle was assayed by flow cytometry (FCM). Results The IKKα was tested higher in three ER-negative breast cancer cell lines than in MCF-7.The influence caused by epidermal growth factor (EGF), tumor necrosis factor (TNF )-α and E_2 to tumor cells′ proliferation was tested. EGF could remarkably enhance cyclin D_1 expression about 83% more in EGF group than that in control group and proliferation index from 0.22 to 0.31( P 0.01). On the other hand, TNF-α inhibited cyclin D_1 expression. Protein kinase C inhibitor, Go6976, could peculiarly prevent NF-κB over-expression caused by EGF. The cell-cycle was assayed by FCM in phase G_0/ G_1 69.36% and in phase S 22.77% when adding EGF and in phase G_0/ G_1 91.54% and in phase S 7.81% when adding EGF and Go6976. The proliferation index decreased from 0.31 to 0.09 ( P 0.01). Conclusions EGF-EGFR pathway can provide ER-negative breast cancer cells the signal for the autonomous growth. This signal promoted tumor cells′ proliferation is transmitted by activating NF-κB and expressing more cyclin D_1. In this pathway, NF-κB play an important role as signal transmitting. The strategy to NF-κB activating may provide new way to treat ER-negative breast cancers.