BLT2 Up-Regulates Interleukin-8 Production and Promotes the Invasiveness of Breast Cancer Cells
- Authors
- Kim, Hyunju; Choi, Jung-A; Park, Geun-Soo; Kim, Jae-Hong
- Issue Date
- 7-11월-2012
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.7, no.11
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLOS ONE
- Volume
- 7
- Number
- 11
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/106951
- DOI
- 10.1371/journal.pone.0049186
- ISSN
- 1932-6203
- 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-kappa B. 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-kappa B 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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Collections - College of Life Sciences and Biotechnology > Division of Life Sciences > 1. Journal Articles
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