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J Breast Cancer. 2018 Mar;21(1):21-27. doi: 10.4048/jbc.2018.21.1.21. Epub 2018 Mar 23.

Berberine Suppresses Fibronectin Expression through Inhibition of c-Jun Phosphorylation in Breast Cancer Cells.

Journal of breast cancer

Yisun Jeong, Daeun You, Hyun-Gu Kang, Jonghan Yu, Seok Won Kim, Seok Jin Nam, Jeong Eon Lee, Sangmin Kim

Affiliations

  1. Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea.
  2. Breast Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  3. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

PMID: 29628980 PMCID: PMC5880962 DOI: 10.4048/jbc.2018.21.1.21

Abstract

PURPOSE: The exact mechanism regulating fibronectin (FN) expression in breast cancer cells has not been fully elucidated. In this study, we investigated the pharmacological mechanism of berberine (BBR) with respect to FN expression in triple-negative breast cancer (TNBC) cells.

METHODS: The clinical significance of FN mRNA expression was analyzed using the Kaplan-Meier plotter database (http://kmplot.com/breast). FN mRNA and protein expression levels were analyzed by real-time polymerase chain reaction and western blotting, respectively.

RESULTS: Using publicly available clinical data, we observed that high FN expression was associated with poor prognosis in patients with breast cancer. FN mRNA and protein expression was increased in TNBC cells compared with non-TNBC cells. As expected, recombinant human FN significantly induced cell spreading and adhesion in MDA-MB231 TNBC cells. We also investigated the regulatory mechanism underlying FN expression. Basal levels of FN mRNA and protein expression were downregulated by a specific activator protein-1 (AP-1) inhibitor, SR11302. Interestingly, FN expression in TNBC cells was dose-dependently decreased by BBR treatment. The level of c-Jun phosphorylation was also decreased by BBR treatment.

CONCLUSION: Our findings demonstrate that FN expression is regulated via an AP-1-dependent mechanism, and that BBR suppresses FN expression in TNBC cells through inhibition of AP-1 activity.

Keywords: Berberine; Cell adhesion; Fibronectins; Transcription factor AP-1

Conflict of interest statement

CONFLICT OF INTEREST: The authors declare that they have no competing interests.

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