GATA4 is highly expressed in childhood acute lymphoblastic leukemia, promotes cell proliferation and inhibits apoptosis by activating BCL2 and MDM2

Mol Med Rep. 2017 Nov;16(5):6290-6298. doi: 10.3892/mmr.2017.7369. Epub 2017 Aug 28.

Abstract

Members of the GATA‑binding factor protein family, including GATA1, GATA2 and GATA3, serve an inhibiting role in leukemia. The present study demonstrated that GATA4 was upregulated in children with acute lymphoblastic leukemia (ALL). Results from a number of functional experiments, including cell proliferation analysis, cell cycle analysis, cell apoptosis assay and Transwell migration and invasion analyses, have suggested that high expression of GATA4 may facilitate proliferation and metastasis, and suppress apoptosis in ALL cells. Chromatin immunoprecipitation assay and luciferase reporter assay revealed that GATA4 was a transcription factor that activated mouse double minute 2 homolog (MDM2) and B cell lymphoma 2 (BCL2) expression in ALL cells. BCL2 is a key anti‑apoptosis protein that was demonstrated to suppress cell apoptosis. In addition, GATA4 was revealed to regulate p53 through the transcriptional activation of MDM2, subsequently influencing cell cycle and apoptosis. Results from the present study suggested that GATA4 may be a key marker in ALL diagnosis and a potential target of molecular therapy.

MeSH terms

  • Apoptosis / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • GATA4 Transcription Factor / genetics*
  • Gene Expression Regulation / genetics*
  • Humans
  • Jurkat Cells
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Signal Transduction / genetics
  • Transcriptional Activation / genetics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • BCL2 protein, human
  • GATA4 Transcription Factor
  • GATA4 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2