RGD Reference Report - Interaction of aryl hydrocarbon receptor and NF-kappaB subunit RelB in breast cancer is associated with interleukin-8 overexpression. - Rat Genome Database

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Interaction of aryl hydrocarbon receptor and NF-kappaB subunit RelB in breast cancer is associated with interleukin-8 overexpression.

Authors: Vogel, CF  Li, W  Wu, D  Miller, JK  Sweeney, C  Lazennec, G  Fujisawa, Y  Matsumura, F 
Citation: Vogel CF, etal., Arch Biochem Biophys. 2011 Aug 1;512(1):78-86. doi: 10.1016/j.abb.2011.05.011. Epub 2011 May 26.
RGD ID: 7777150
Pubmed: PMID:21640702   (View Abstract at PubMed)
PMCID: PMC3135412   (View Article at PubMed Central)
DOI: DOI:10.1016/j.abb.2011.05.011   (Journal Full-text)

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)alpha-negative human breast tumors and that its overexpression is positively correlated to that of the NF-kappaB 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 ERalpha 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
breast cancer  IEP 7777150protein:increased expression:breastRGD 
breast cancer  ISORELB (Homo sapiens)7777150; 7777150protein:increased expression:breastRGD 

Objects Annotated

Genes (Rattus norvegicus)
Relb  (RELB proto-oncogene, NF-kB subunit)

Genes (Mus musculus)
Relb  (avian reticuloendotheliosis viral (v-rel) oncogene related B)

Genes (Homo sapiens)
RELB  (RELB proto-oncogene, NF-kB subunit)


Additional Information