Oncotarget

Research Papers:

The implication from RAS/RAF/ERK signaling pathway increased activation in epirubicin treated triple negative breast cancer

Jianbo Huang, Qingqing Luo, Yun Xiao, Hongyuan Li, Lingquan Kong and Guosheng Ren _

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Oncotarget. 2017; 8:108249-108260. https://doi.org/10.18632/oncotarget.22604

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Abstract

Jianbo Huang1,*, Qingqing Luo1,*, Yun Xiao2,*, Hongyuan Li1, Lingquan Kong1 and Guosheng Ren1

1Department of Endocrine & Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

2Department of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China

*These authors have contributed equally to this work

Correspondence to:

Guosheng Ren, email: rengs726@126.com

Lingquan Kong, email: huihuikp@163.com

Keywords: TNBC; RAS/RAF/ERK signaling pathway; GSEA; epirubicin; targeting therapy

Received: July 20, 2017     Accepted: October 28, 2017     Published: November 21, 2017

ABSTRACT

Background: Triple negative breast cancer (TNBC) is not sensitive to RAS/RAF/ERK signaling pathway (ERK pathway) targeting therapy, due to the absence of excessive activation of ERK pathway. However, the kinase cascades might be activated after chemotherapy in TNBC. Here we aimed to predict whether ERK pathway targeting therapy could be used as an adjuvant therapy in TNBC.

Methods: Within online GEO datasets (GSE43816 and GSE54326), gene set enrichment analysis (GSEA) was performed to detect molecular changes in epirubicin treated TNBC samples and cells, ERK pathway components and regulation genes changes were included.

Results: In epirubicin treated TNBC samples and cells, we found ERK pathway components (eg. MAPK13, MAP3K1, MAPK12, MAPK11 and MAPKAPK3) were obviously enriched, also, expression of ERK pathway positive regulation genes significantly increased (P<0.05) and negative regulation genes decreased (P<0.05) in epirubicin resistant cells. Moreover, phosphorylated ERK levels were significantly elevated in MDA-MB-231 cells after epirubicin treatment.

Conclusion: ERK signaling pathway was more activated in epirubicin treated TNBC, possibly contributing to the epirubicin resistance in TNBC, it implicated that ERK pathway could be used as an novel candidate for targeting therapy in refractory and relapse TNBC.


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