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PLoS One. 2012;7(11):e49186. doi: 10.1371/journal.pone.0049186. Epub 2012 Nov 7.

BLT2 up-regulates interleukin-8 production and promotes the invasiveness of breast cancer cells.

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  • 1School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.

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.

PMID:
23145117
[PubMed - indexed for MEDLINE]
PMCID:
PMC3492316
Free PMC Article
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