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Article Abstract

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 ( < 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141113PMC
http://dx.doi.org/10.2147/OTT.S160531DOI Listing

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