title: Nuclear factor-ĸB plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells.
abstract: Since more than 75% of breast cancers overexpress estrogen receptors (ER), endocrine therapy targeting ER has significantly improved the survival rate. Nonetheless, breast cancer still afflicts women worldwide and the major problem behind it is resistance to endocrine therapy. We have previously shown the involvement of nuclear factor-κB (NF-κB) in neoplastic proliferation of human breast cancer cells; however, the association with the transformation of ER-positive cells remains unclear. In the current study, we focused on roles of NF-κB in the hormone dependency of breast cancers by means of ER-positive MCF-7 cells. Blocking of NF-κB signals in ER-negative cells stopped proliferation by downregulation of D-type cyclins. In contrast, the MCF-7 cells were resistant to NF-κB inhibition. Under estrogen-free conditions, the ER levels were reduced when compared with the original MCF-7 cells and the established cell subline exhibited tamoxifen resistance. Additionally, NF-κB participated in cell growth instead of the estrogen-ER axis in the subline and consequently, interfering with the NF-κB signals induced additive anticancer effects with tamoxifen. MMP-9 production responsible for cell migration, as well as the cell expansion in vivo, were suppressed by NF-κB inhibition. Therefore, we suggest that NF-κB is a master switch in both ER-positive and ER-negative breast cancers.
authors: 1] Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan [2] Comparative Medicine, Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University of Vienna, University of Vienna, Veterinaerplatz 1, 1210 Vienna, Austria.
authors: Kumiko
authors: K
authors: Oida
authors: Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors: Akira
authors: A
authors: Matsuda
authors: Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors: Kyungsook
authors: K
authors: Jung
authors: Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors: Yan
authors: Y
authors: Xia
authors: Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors: Hyosun
authors: H
authors: Jang
authors: Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors: Yosuke
authors: Y
authors: Amagai
authors: Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors: Ginnae
authors: G
authors: Ahn
authors: Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors: Sho
authors: S
authors: Nishikawa
authors: Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors: Saori
authors: S
authors: Ishizaka
authors: 1] Comparative Medicine, Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University of Vienna, University of Vienna, Veterinaerplatz 1, 1210 Vienna, Austria [2] Comparative Immunology and Oncology, Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors: Erika
authors: E
authors: Jensen-Jarolim
authors: 1] Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan [2] Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors: Hiroshi
authors: H
authors: Matsuda
authors: 1] Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan [2] Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
authors: Akane
authors: A
authors: Tanaka
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000627:therapeutic use / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use / Q000633:toxicity*; D014183:Transplantation, Heterologous
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D013629:Tamoxifen; C492919:N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide; D020780:Matrix Metalloproteinase 9