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: Kumiko Oida, Akira Matsuda, Kyungsook Jung, Yan Xia, Hyosun Jang, Yosuke Amagai, Ginnae Ahn, Sho Nishikawa, Saori Ishizaka, Erika Jensen-Jarolim, Hiroshi Matsuda, Akane Tanaka
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 4057 (Feb 17 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 24531845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Benzamides
• NF-kappa B
• RNA, Small Interfering
• Receptors, Estrogen
• Tamoxifen
• N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide
• Matrix Metalloproteinase 9

Topics

• Animals
• Antineoplastic Agents, Hormonal (therapeutic use, toxicity)
• Apoptosis (drug effects)
• Benzamides (therapeutic use, toxicity)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Drug Resistance, Neoplasm
• Female
• Humans
• MCF-7 Cells
• Matrix Metalloproteinase 9
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• NF-kappa B (antagonists & inhibitors, genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Receptors, Estrogen (metabolism)
• Tamoxifen (therapeutic use, toxicity)
• Transplantation, Heterologous