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Updated: Nov 21, 2025

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

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

Shaoting Zhang1, Guangrong Zhu1, Jun Shi1

  • 1Department of Pathogenic Biology and Medical Immunology, School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, China.

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology
|January 14, 2021
PubMed

Insights

Phosphatidylinositol 3-kinase (PI3K) isoforms play distinct roles in KIT mutation signaling. PI3Kδ is key in BaF3 cells, while PI3Kβ is crucial in GIST-T1 cells for KIT activation and downstream signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Type III receptor tyrosine kinase KIT mutations drive gastrointestinal stromal tumors (GIST).
  • Phosphatidylinositol 3-kinase (PI3K) signaling pathways are implicated in cancer cell proliferation and survival.
  • Understanding the specific roles of PI3K isoforms in KIT-mutated cancers is crucial for targeted therapy development.

Purpose of the Study:

  • To elucidate the differential roles of PI3K isoforms (PI3Kα, PI3Kβ, PI3Kδ) in mediating signaling downstream of wild-type and mutant KIT.
  • To investigate how these PI3K isoforms influence cell proliferation and apoptosis in KIT-mutated GIST models.

Main Methods:

  • Stable expression of wild-type KIT and common GIST mutations (V560D, W557K558del) in BaF3 cells.
  • Treatment with specific PI3K isoform inhibitors (PI3Kα, PI3Kβ, PI3Kδ) and a pan-PI3K inhibitor.
  • Detection of KIT activation and downstream signaling (AKT, ERK) via immunoprecipitation and Western blot.
  • Assessment of cell proliferation (MTT assay) and apoptosis (flow cytometry) in GIST-T1 cells.

Main Results:

  • In BaF3 cells, PI3Kδ inhibition most effectively suppressed KIT activation and downstream signaling (AKT, ERK).
  • In GIST-T1 cells, PI3Kβ inhibition demonstrated the strongest effect on KIT signaling, followed by PI3Kδ and PI3Kα.
  • Differential sensitivity of KIT signaling to PI3K isoform inhibitors was observed between BaF3 and GIST-T1 cell lines.

Conclusions:

  • PI3Kδ plays a predominant role in KIT activation and downstream signaling in BaF3 cells.
  • PI3Kβ is the major contributor to KIT activation and downstream signaling in GIST-T1 cells.
  • PI3K isoforms exhibit cell-type-specific functions in KIT mutation-mediated cell transformation, highlighting the need for context-dependent therapeutic strategies.

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