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Tumor Biology

, Volume 37, Issue 4, pp 4991–4999 | Cite as

MEK-dependent IL-8 induction regulates the invasiveness of triple-negative breast cancer cells

  • Sangmin Kim
  • Jeongmin Lee
  • Myeongjin Jeon
  • Jeong Eon Lee
  • Seok Jin Nam
Original Article

Abstract

Interleukin-8 (IL-8) serves as a prognostic marker for breast cancer, and its expression level correlates with metastatic breast cancer and poor prognosis. Here, we investigated the levels of IL-8 expression in a variety of breast cancer cells and the regulatory mechanism of IL-8 in triple-negative breast cancer (TNBC) cells. Our results showed that IL-8 expression correlated positively with overall survival in basal-type breast cancer patients. The levels of IL-8 mRNA expression and protein secretion were significantly increased in TNBC cells compared with non-TNBC cells. In addition, the invasiveness of the TNBC cells was dramatically increased by IL-8 treatment and then augmented invasion-related proteins such as matrix metalloproteinase (MMP)-2 or MMP-9. We observed that elevated IL-8 mRNA expression and protein secretion were suppressed by a specific MEK1/2 inhibitor, UO126. In contrast, the overexpression of constitutively active MEK significantly increased the level of IL-8 mRNA expression in BT474 non-TNBC cells. Finally, we investigated the effect of UO126 on the tumorigenecity of TNBC cells. Our results showed that anchorage-independent growth, cell invasion, and cell migration were also decreased by UO126 in TNBC cells. As such, we demonstrated that IL-8 expression is regulated through MEK/ERK-dependent pathways in TNBC cells. A diversity of MEK blockers, including UO126, may be promising for treating TNBC patients.

Keywords

IL-8 Poor prognosis Cell invasion MEK Triple-negative breast cancer 

Notes

Acknowledgments

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and funded by the Ministry of Health & Welfare, Republic of Korea (HI14C3418), and by a Samsung Biomedical Research Institute grant (SMX1131701).

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2015_4345_Fig6_ESM.gif (11 kb)
Supplement 1

The co-relation between IL-8 expression and relapse-free survival in luminal B- and HER2-type breast cancer patients. We analyzed the clinical value of IL-8 in luminal B- and HER2-type breast cancer patients using a public database [Kaplan–Meier plotter database (http://kmplot.com/breast)]. (A) Relapse-free survival of luminal B type breast cancer patients. (B) Relapse-free survival of HER2 type breast cancer patients. Lum: Luminal. (GIF 10 kb)

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High resolution image (TIF 103 kb)
13277_2015_4345_Fig7_ESM.gif (15 kb)
Supplement 2

IL-8-induced cell invasion is suppressed by SB225002 in MDA-MB231 cells. (A) We analyzed the levels of MEK and ERK phosphorylation using whole cell lysates in BT474 and MDA-MB231 cells. The levels of phospho-MEK, phospho-ERK, and β-actin expression were analyzed by western blotting. (B) MDA-MB231 cells was pretreated with 10 μM SB225002 for 30 min and then treated with 20 ng/ml IL-8 for 16 h. The cells on the bottom side of the filter were fixed and stained. Cell morphology was analyzed using a CK40 inverted microscope. These results are representative of three independent experiments. Con: control, SB: SB225002. (GIF 14 kb)

13277_2015_4345_MOESM2_ESM.tif (203 kb)
High resolution image (TIF 203 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Surgery, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  2. 2.Department of Health Sciences and TechnologySamsung Advanced Institute for Health Sciences and TechnologySeoulSouth Korea

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