title: Interaction of aryl hydrocarbon receptor and NF-κB subunit RelB in breast cancer is associated with interleukin-8 overexpression.
abstract: The aryl hydrocarbon receptor (AhR) has been best known for its role in mediating the toxicity of dioxin. Here we show that AhR overexpression is found among estrogen receptor (ER)α-negative human breast tumors and that its overexpression is positively correlated to that of the NF-κB subunit RelB and Interleukin (IL)-8. Increased DNA binding activity of the AhR and RelB is coupled to IL-8 overexpression in primary breast cancer tissue, which was also supported by in situ hybridization. Activation of AhR in vitro by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced IL-8 expression in MDA-MB 436 and MCF-7 cells in an AhR and RelB dependent manner. Consistently, downregulation of RelB or AhR by small interfering RNAs (siRNA) decreased the level of IL-8 but increased expression of ERα in vitro in MCF-7 cells. Our results strongly suggest that RelB and AhR have a critical role in the regulation of IL-8 and reveal a supportive role of RelB and AhR in the anti-apoptotic response in human breast cancer cells. AhR and RelB may present a novel therapeutic target for inflammatory driven breast carcinogenesis and tumor progression. Overexpression of pro-survival factors AhR and RelB may explain the process of the development of environmentally-induced type of breast cancers.
authors.affiliation: Department of Environmental Toxicology, University of California Davis, One Shields Avenue, CA 95616, USA. cfvogel@ucdavis.edu
authors.forename: Christoph Franz Adam
authors.initials: CF
authors.lastname: Vogel
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Dalei
authors.initials: D
authors.lastname: Wu
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Miller
authors.forename: Colleen
authors.initials: C
authors.lastname: Sweeney
authors.forename: Gwendal
authors.initials: G
authors.lastname: Lazennec
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsumura
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D047628:Estrogen Receptor alpha; D016209:Interleukin-8; D016328:NF-kappa B; C497593:RELB protein, human; D018336:Receptors, Aryl Hydrocarbon; D051841:Transcription Factor RelB; D004247:DNA