Overexpression of PTPN21 promotes proliferation of EGF-stimulated acute lymphoblastic leukemia cells via the MAPK signaling pathways.

IF 2 4区医学 Q3 HEMATOLOGY Hematology Pub Date : 2024-12-01 Epub Date: 2024-05-24 DOI:10.1080/16078454.2024.2356292

Ni Zhu, Jieping Wei, Li-Mengmeng Wang, He Huang, Haowen Xiao

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Abstract

Objectives: This study aims to investigate the role of excessive Protein Tyrosine Phosphatase Non-Receptor Type 21 (PTPN21) in the proliferation of Acute Lymphoblastic Leukemia (ALL) cells with EGF stimulation.

Methods: PTPN21 was overexpressed in ALL cell lines by lentiviral transfection. Apoptosis was assayed by Annexin V/7-AAD staining. The proliferation and cell cycle of EGF-treated ALL cells were assessed by MTT and Ki-67/7-AAD staining respectively. The phosphorylation of Src tyrosine kinase and mediators of distinct MAPK pathways were assessed by Western blot.

Results: Overexpression of PTPN21 had minimal effect on the apoptosis of ALL cells, but significantly promoted the proliferation and cell cycle progression of ALL cells stimulated with EGF. The activity of Src tyrosine kinase and the MAPK pathways was elevated. Inhibition of MAPK pathways by specific inhibitors mitigated this pro-proliferative effect of excessive PTPN21 on EGF-stimulated ALL cells.

Conclusion: PTPN21 may facilitate ALL progression by promoting cell proliferation via the Src/MAPK signaling pathways.

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过表达 PTPN21 可通过 MAPK 信号通路促进 EGF 刺激的急性淋巴细胞白血病细胞的增殖。

研究目的本研究旨在探讨在 EGF 刺激下，过量蛋白酪氨酸磷酸酶非受体 21 型（PTPN21）在急性淋巴细胞白血病（ALL）细胞增殖中的作用：方法：通过慢病毒转染在ALL细胞系中过表达PTPN21。方法：通过慢病毒转染在ALL细胞系中过表达PTPN21，用Annexin V/7-AAD染色检测细胞凋亡。EGF处理的ALL细胞的增殖和细胞周期分别通过MTT和Ki-67/7-AAD染色进行评估。通过Western印迹评估了Src酪氨酸激酶和不同MAPK通路介质的磷酸化情况：结果：过表达PTPN21对ALL细胞的凋亡影响很小，但却能显著促进EGF刺激下ALL细胞的增殖和细胞周期的进展。Src酪氨酸激酶和MAPK通路的活性升高。通过特异性抑制剂抑制MAPK通路可减轻过量PTPN21对EGF刺激的ALL细胞的增殖效应：结论：PTPN21可通过Src/MAPK信号通路促进细胞增殖，从而促进ALL进展。

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来源期刊

Hematology 医学-血液学

CiteScore

2.60

自引率

5.30%

发文量

140

审稿时长

3 months

期刊介绍： Hematology is an international journal publishing original and review articles in the field of general hematology, including oncology, pathology, biology, clinical research and epidemiology. Of the fixed sections, annotations are accepted on any general or scientific field: technical annotations covering current laboratory practice in general hematology, blood transfusion and clinical trials, and current clinical practice reviews the consensus driven areas of care and management.