The nuclear factor kappa B activation: the key step of cell proliferation in estrogen receptor-negative breast cancer cells.
- Author:
Han-jin WANG
1
;
Zheng-yan WU
;
Ping FAN
;
Jian-min BIAN
Author Information
- Publication Type:Journal Article
- MeSH: Breast Neoplasms; metabolism; pathology; physiopathology; Carbazoles; pharmacology; Cell Proliferation; drug effects; Cyclin D1; biosynthesis; Epidermal Growth Factor; pharmacology; Estradiol; pharmacology; Female; Humans; I-kappa B Kinase; metabolism; Indoles; pharmacology; NF-kappa B; metabolism; physiology; Receptors, Estrogen; metabolism; Signal Transduction; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; pharmacology
- From: Chinese Journal of Surgery 2005;43(15):1014-1016
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSThe protein of IkappaB kinase alpha (IKKalpha) was measured by Western blot and the influence on cell-cycle was assayed by flow cytometry (FCM).
RESULTSThe 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).
CONCLUSIONSEGF-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.