BLT2 Up-Regulates Interleukin-8 Production and Promotes the Invasiveness of Breast Cancer Cells

Hyunju Kim, Jung A. Choi, Geun Soo Park, Jae-Hong Kim

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: The elevated production of interleukin (IL)-8 is critically associated with invasiveness and metastatic potential in breast cancer cells. However, the intracellular signaling pathway responsible for up-regulation of IL-8 production in breast cancer cells has remained unclear. Methodology/Principal Findings: In this study, we report that the expression of BLT2 is markedly up-regulated in the highly aggressive human breast cancer cell lines MDA-MB-231 and MDA-MB-435 compared with MCF-10A immortalized human mammary epithelial cells, as determined by RT-PCR, real-time PCR and FACS analysis. Blockade of BLT2 with BLT2 siRNA knockdown or BLT2 inhibitor treatment downregulated IL-8 production and thereby diminished the invasiveness of aggressive breast cancer cells, analyzed by Matrigel invasion chamber assays. We further characterized the downstream signaling mechanism by which BLT2 stimulates IL-8 production and identified critical mediatory roles for the generation of reactive oxygen species (ROS) and the consequent activation of the transcription factor NF-κB. Moreover, blockade of BLT2 suppressed the formation of metastatic lung nodules by MDA-MB-231 cells in both experimental and orthotopic metastasis models. Conclusions/Significance: Taken together, our study demonstrates that a BLT2-ROS-NF-κB pathway up-regulates IL-8 production in MDA-MB-231 and MDA-MB-435 cells, thereby contributing to the invasiveness of these aggressive breast cancer cells. Our findings provide insight into the molecular mechanism of invasiveness in breast cancer.

Original languageEnglish
Article numbere49186
JournalPLoS One
Volume7
Issue number11
DOIs
Publication statusPublished - 2012 Nov 7

Fingerprint

interleukin-8
Interleukin-8
breast neoplasms
Up-Regulation
Cells
Breast Neoplasms
Reactive Oxygen Species
reactive oxygen species
Small Interfering RNA
small interfering RNA
Assays
Transcription Factors
metastasis
Chemical activation
breasts
neoplasm cells
Real-Time Polymerase Chain Reaction
quantitative polymerase chain reaction
Breast
epithelial cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

BLT2 Up-Regulates Interleukin-8 Production and Promotes the Invasiveness of Breast Cancer Cells. / Kim, Hyunju; Choi, Jung A.; Park, Geun Soo; Kim, Jae-Hong.

In: PLoS One, Vol. 7, No. 11, e49186, 07.11.2012.

Research output: Contribution to journalArticle

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abstract = "Background: The elevated production of interleukin (IL)-8 is critically associated with invasiveness and metastatic potential in breast cancer cells. However, the intracellular signaling pathway responsible for up-regulation of IL-8 production in breast cancer cells has remained unclear. Methodology/Principal Findings: In this study, we report that the expression of BLT2 is markedly up-regulated in the highly aggressive human breast cancer cell lines MDA-MB-231 and MDA-MB-435 compared with MCF-10A immortalized human mammary epithelial cells, as determined by RT-PCR, real-time PCR and FACS analysis. Blockade of BLT2 with BLT2 siRNA knockdown or BLT2 inhibitor treatment downregulated IL-8 production and thereby diminished the invasiveness of aggressive breast cancer cells, analyzed by Matrigel invasion chamber assays. We further characterized the downstream signaling mechanism by which BLT2 stimulates IL-8 production and identified critical mediatory roles for the generation of reactive oxygen species (ROS) and the consequent activation of the transcription factor NF-κB. Moreover, blockade of BLT2 suppressed the formation of metastatic lung nodules by MDA-MB-231 cells in both experimental and orthotopic metastasis models. Conclusions/Significance: Taken together, our study demonstrates that a BLT2-ROS-NF-κB pathway up-regulates IL-8 production in MDA-MB-231 and MDA-MB-435 cells, thereby contributing to the invasiveness of these aggressive breast cancer cells. Our findings provide insight into the molecular mechanism of invasiveness in breast cancer.",
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