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A correlation study of the expression of HA-CD44st and HER-2 in breast cancer

Authors Ying Zhi L, Xu Z, Ning L, Jia Jin L, Hai Cui Y, Hong HG, Fang XJ

Received 21 December 2017

Accepted for publication 25 April 2018

Published 10 September 2018 Volume 2018:11 Pages 5677—5688

DOI https://doi.org/10.2147/OTT.S160531

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Samir Farghaly


Lu Ying Zhi,1,* Zhang Xu,2,* Li Ning,3 Li Jia Jin,1,4 Yan Hai Cui,1 Huang Guan Hong,1 Xin Jian Fang1

1Department of Medical Oncology, the Second People’s Hospital of Lianyungang (Lianyungang Hospital Affiliated to Bengbu Medical College), Lianyungang, Jiangsu 222000, People’s Republic of China; 2Molecular Biology Laboratory, Medical College, Jiangsu University, Jiangsu 2012013, People’s Republic of China; 3Department of Surgery, the First People’s Hospital of Lianyungang, Jiangsu 222000, People’s Republic of China; 4Department of Information Center, the Second People’s Hospital of Lianyungang (Lianyungang Hospital Affiliated to Bengbu Medical College), Lianyungang, Jiangsu 222000, People’s Republic of China

*These authors contributed equally to this work

Background: This study investigated the effect of hyaluronic acid (HA)-CD44st on the invasive ability of human breast cancer MCF-7 cells and the correlation between the expression of CD44st and human epidermal growth factor receptor-2 (HER-2) in postoperative breast cancer patients.
Materials and methods: MCF-7 cells transfected with the eukaryotic expression vector pcDNA3.1-CD44st (MCF/CD44st) were used to examine the effect of the activation of the HA-CD44st-transforming growth factor β (TGFβ)-phosphatidylinositol-3-kinase (PI3K) signaling pathway on the invasive ability of MCF-7 cells. The expression of proteins related to this signaling pathway was assessed by flow cytometry, reverse transcription-polymerase chain reaction, and Western blotting, and the role of AP-1 in the pathway was investigated by electrophoretic mobility shift assay. The effect of pathway activation on the invasion of MCF-7 cells was assessed by Transwell assay, and CD44 expression in breast cancer tissue was detected by immunohistochemistry. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression of CD44st and HER-2 in breast cancer tissue and their correlation was investigated.
Results: HA significantly upregulated HER-2 and TGFβ in MCF-7/CD44st cells, increased p-AKT expression and AP-1 activity, and promoted the invasive ability of tumor cells. CD44st mRNA expression had significant difference between breast cancer tissues and adjacent normal tissues (P < 0.05), and high expression of CD44st mRNA was closely correlated with HER-2 expression in breast cancer tissues.
Conclusion: Binding of HA to the CD44st receptor may regulate the invasiveness of MCF-7 cells through the CD44st/TGFβ/PI3K/AP-1 signaling pathway with increased expression of TGFβ and HER-2. The expression of CD44st mRNA is correlated with HER-2 expression in postoperative breast cancer patients.

Keywords: CD44st, TGFβ, HER-2, invasion, breast cancer

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