[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-kappaB) activation and the mechanism of NF-kappaB-promoted proliferation in estrogen receptor (ER)-negative breast cancer cells.


METHODS
The protein of IkappaB kinase alpha (IKKalpha) was measured by Western blot and the influence on cell-cycle was assayed by flow cytometry (FCM).


RESULTS
The IKKalpha 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)-alpha 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-alpha inhibited cyclin D(1) expression. Protein kinase C inhibitor, Go6976, could peculiarly prevent NF-kappaB 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-kappaB and expressing more cyclin D(1). In this pathway, NF-kappaB play an important role as signal transmitting. The strategy to NF-kappaB activating may provide new way to treat ER-negative breast cancers.
Wang
Han-jin
HJ
Department of General Surgery, the First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. whj_888@sohu.com
Wu
Zheng-yan
ZY
Fan
Ping
P
Bian
Jian-min
JM
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002227:Carbazoles / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002227:Carbazoles; D007211:Indoles; D016328:NF-kappa B; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; C081021:Go 6976; D019938:Cyclin D1; D004958:Estradiol; D004815:Epidermal Growth Factor; D051550:I-kappa B Kinase