International Journal of Medical Sciences

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9 December 2018

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Int J Med Sci 2018; 15(7):738-747. doi:10.7150/ijms.24981

Research Paper

The suppression of DUSP5 expression correlates with paclitaxel resistance and poor prognosis in basal-like breast cancer

Tieju Liu1,2, Huizhi Sun1, Shiqi Liu1, Zhao Yang1, Linqi Li1, Nan Yao1, Siqi Cheng1, Xueyi Dong1,2, Xiaohui Liang1,2, Chen Chen1, Yi Wang1, Xiulan Zhao1,2✉

1. Department of Pathology, Tianjin Medical University, Tianjin 300070, China
2. Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China

Abstract

Basal-like breast cancer (BLBC) is resistant to endocrinotherapy and targeted therapy and new molecular therapies are needed for BLBC. In this study, we evaluated the role of DUSP1 and DUSP5, negative regulators of mitogen-activated protein kinase pathway, in the aggressiveness of BLBC. MDA-MB-231 cells were given paclitaxel (PTX) treatment and subsequently PTX resistant cell clones were established. Microarray analysis, real-time quantitative reverse transcription PCR (qRT-PCR), and online analysis of large cohorts of breast cancer patients were performed. The PTX resistant cells showed stronger cell proliferation ability by exhibiting the upregulation of CENPF, CDC6, MCM3, CLSPN and SMC1A expression. Furthermore, DUSP1 and DUSP5 expression was significantly downregulated in PTX resistant cells. In addition, in large breast cancer patients' database, both DUSP1 and DUSP5 correlated negatively with higher histological grade. DUSP1 low expression was obvious in HER2 positive and basal like while DUSP5 low expression was peculiar for basal like compared with other subtypes. Remarkably, low expression of DUSP5, but not DUSP1, was significantly correlated with poor survival of BLBC patients. In conclusion, our data suggest that loss of DUSP5 expression results in PTX resistance and tumor progression, providing a rationale for a therapeutic agent that restores DUSP5 in BLBC.

Keywords: basal-like breast cancer, DUSP5, paclitaxel resistance

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How to cite this article:
Liu T, Sun H, Liu S, Yang Z, Li L, Yao N, Cheng S, Dong X, Liang X, Chen C, Wang Y, Zhao X. The suppression of DUSP5 expression correlates with paclitaxel resistance and poor prognosis in basal-like breast cancer. Int J Med Sci 2018; 15(7):738-747. doi:10.7150/ijms.24981. Available from http://www.medsci.org/v15p0738.htm