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

Christoph Franz Adam Vogel, Wen Li, Dalei Wu, Jamie K. Miller, Colleen A Sweeney, Gwendal Lazennec, Yasuko Fujisawa, Fumio Matsumura

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)78-86
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume512
Issue number1
DOIs
StatePublished - Aug 1 2011

Fingerprint

Aryl Hydrocarbon Receptors
Interleukin-8
Breast Neoplasms
MCF-7 Cells
Estrogen Receptors
Tumors
Dioxins
Small Interfering RNA
In Situ Hybridization
Toxicity
Carcinogenesis
Down-Regulation
Chemical activation
Cells
Tissue

Keywords

  • AhR
  • Breast cancer
  • IL-8
  • NF-κB
  • RelB
  • TCDD

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Interaction of aryl hydrocarbon receptor and NF-κB subunit RelB in breast cancer is associated with interleukin-8 overexpression. / Vogel, Christoph Franz Adam; Li, Wen; Wu, Dalei; Miller, Jamie K.; Sweeney, Colleen A; Lazennec, Gwendal; Fujisawa, Yasuko; Matsumura, Fumio.

In: Archives of Biochemistry and Biophysics, Vol. 512, No. 1, 01.08.2011, p. 78-86.

Research output: Contribution to journalArticle

Vogel, Christoph Franz Adam ; Li, Wen ; Wu, Dalei ; Miller, Jamie K. ; Sweeney, Colleen A ; Lazennec, Gwendal ; Fujisawa, Yasuko ; Matsumura, Fumio. / Interaction of aryl hydrocarbon receptor and NF-κB subunit RelB in breast cancer is associated with interleukin-8 overexpression. In: Archives of Biochemistry and Biophysics. 2011 ; Vol. 512, No. 1. pp. 78-86.
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