• J. Investig. Med. · Jun 2022

    Dual-specificity phosphatase 8 (DUSP8) induces drug resistance in breast cancer by regulating MAPK pathways.

    • Hanchao Zhang, Meng Wang, Di Chen, and Chengyu Luo.
    • Department of General Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, Beijing, People's Republic of China.
    • J. Investig. Med. 2022 Jun 1; 70 (5): 1293-1300.

    AbstractThe aim of the study was to explore the role and molecular mechanism of dual-specificity phosphatase 8 (DUSP8) in the drug resistance of trastuzumab in breast cancer. Real-time PCR and western blot detected the difference in expression of DUSP8 between breast cancer tissue/cells and trastuzumab-resistant tissues/cells. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of DUSP8 in breast cancer. si-DUSP8 or dusp8 overexpression vector was transiently transfected, and the effects of si-DUSP8 on apoptosis, cell viability and cell migration of drug-resistant cell lines were investigated by flow cytometry, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) and Transwell assays, and its regulation mechanism finally explored. The results showed that the expression of DUSP8 in breast cancer tissues and cells was significantly higher than in matched non-tumor tissues and cells. DUSP8 was significantly upregulated in non-responsive patients compared with patients who responded to trastuzumab. ROC analysis showed that the area under the curve was 0.732, and the diagnostic sensitivity and specificity were 64.86% and 75.76%. DUSP8 knockdown promotes apoptosis and reduces trastuzumab resistance in BT474/TR and SKBR3/TR cells by inhibiting cell migration and cell viability. Knockdown of DUSP8 increased the expression of p-p38 and p-ERK, and the regulation of DUSP8 in chemotherapy resistance of breast cancer cells may be realized by mediating mitogen-activated protein kinase (MAPK)-related signaling pathways. In conclusion, knockdown of DUSP8 expression in trastuzumab-resistant cells can inhibit cell migration and proliferation, and leads to decreased drug resistance by activating MAPK signaling pathway in trastuzumab-resistant cells.© American Federation for Medical Research 2022. No commercial re-use. See rights and permissions. Published by BMJ.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…