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01-04-2016 | Original Article

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

Authors: Sangmin Kim, Jeongmin Lee, Myeongjin Jeon, Jeong Eon Lee, Seok Jin Nam

Published in: Tumor Biology | Issue 4/2016

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.

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Title: MEK-dependent IL-8 induction regulates the invasiveness of triple-negative breast cancer cells
Authors: Sangmin Kim
Jeongmin Lee
Myeongjin Jeon
Jeong Eon Lee
Seok Jin Nam
Publication date: 01-04-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 4/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4345-7

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