PI3K isoforms PI3Kβ and PI3Kδ play different roles in KIT mutation-mediated cell transformation].

Shaoting Zhang, Guangrong Zhu, Jun Shi, Jihui Yang, Zongying Jiang, Liangying Zhang, Kaikai Dou, Jianmin Sun

Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 2021 Jan

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Objective To investigate the role of phosphatidylinositol 3-kinase (PI3K) isoforms in type III receptor tyrosine kinase KIT mutation-mediated signaling and cell proliferation. Methods The wild-type KIT and the common KIT mutations V560D and W557K558del in gastrointestinal stromal tumors (GIST) were stably expressed in BaF3 cells. The cells were treated with PI3K isoforms PI3Kα, PI3Kβ and PI3Kδ specific inhibitors or pan PI3K inhibitor. The activation of KIT and its downstream signals was detected by immunoprecipitation and Western blot analysis. GIST-T1 cells were treated with the same drug, and the activation of KIT and its downstream signals was also detected by immunoprecipitation and Western blot analysis, and cell proliferation and apoptosis were detected by MTT assay and flow cytometry, respectively. Results Compared with the controls, in BaF3 cells expressing wild-type KIT and its mutants, the activation of KIT and its downstream signaling molecules AKT and ERK was inhibited the most by PI3Kδ specific inhibitor, followed by the specific inhibitors of PI3Kα and PI3Kβ subtype. In GIST-T1 cells, the activation of KIT and its downstream signals was inhibited the most by PI3Kβ specific inhibitor, followed by PI3Kδ and PI3Kα specific inhibitors. Conclusion In BaF3 cells, PI3Kδ subtype plays a major role in KIT activation and its downstream signal transduction, while in GIST-T1 cells, PI3Kβ subtype plays a major role in KIT activation and its downstream signal transduction. These results indicate that PI3K isoforms play different roles in KIT mutation-mediated cell transformation depending on the host cells.

Citation

Shaoting Zhang, Guangrong Zhu, Jun Shi, Jihui Yang, Zongying Jiang, Liangying Zhang, Kaikai Dou, Jianmin Sun. PI3K isoforms PI3Kβ and PI3Kδ play different roles in KIT mutation-mediated cell transformation]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology. 2021 Jan;37(1):39-46