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Notch signaling maintains proliferation and survival of the HL60 human promyelocytic leukemia cell line and promotes the phosphorylation of the Rb protein

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Abstract

The Notch signaling pathway has been implicated in the development of several leukemia and lymphoma. In order to investigate the relationship between Notch signaling and acute myeloid leukemia (AML), in this study, we expressed a recombinant Notch ligand protein, the DSL domain of the human Jagged1 fused with GST (GST-Jag1). GST-Jag1 could activate Notch signaling in the human promyelocytic leukemia cell line HL60, as shown by a reporter assay and the induced expression of Notch effector gene Hes1 and Hes5. However, GST-Jag1 had no effect on the proliferation and survival of HL60 cells. HL60 cells expressed both Notch ligands and receptors, and had a potential of reciprocal stimulation of Notch signaling between cells. We, therefore, blocked Notch signaling in cultured HL60 cells using a γ-secretase inhibitor (GSI). We found that GSI inhibited the proliferation of HL60 cells significantly by blocking the cell-cycle progression in the G1 phase. Furthermore, GSI induced remarkably apoptosis of HL60 cells. These changes in GSI-treated HL60 cells correlated with the down-regulation of c-Myc and Bcl2, and the low phosphorylation of the Rb protein. These results suggested that reciprocal Notch signaling might be necessary for the proliferation and survival of AML cells, possibly through the maintenance of the expression of c-Myc and Bcl2, as well as the phosphorylation of the Rb protein.

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Acknowledgments

We thank Ms Hui Wang for English editing of the manuscript. This study was supported by grants from the National Natural Science Foundation of China (30370598, 30425015, 30400079, 30600544), the PCSIRT program (IRT0459) of the Ministry of Education of China, and the Ministry of Science and Technology of China (2006AA02A111, 2009CB521706).

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Authors and Affiliations

  1. Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China

    Guo-Hui Li, Dan-Dan Yin, Si-Yong Huang, Zhi-Jie Kang, Heng Xu, Qiang Liu, Yan-Lan Wu, Xiao-Li Niu, Li Zhang, Li Liu, Miao-Wang Hao, Hua Han & Ying-Min Liang

  2. Department of Traditional Chinese Medicine, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China

    Yu-Zhen Fan

  3. State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xi’an, 710032, China

    Xiao-Wei Liu, Bing-Fang Zhang, Dan-Dan Yin, Fei He, Qiang Liu & Hua Han

  4. Department of Gereology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Bing-Fang Zhang

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  1. Guo-Hui Li
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  2. Yu-Zhen Fan
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  9. Heng Xu
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  13. Li Zhang
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  14. Li Liu
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  15. Miao-Wang Hao
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  16. Hua Han
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  17. Ying-Min Liang
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Corresponding authors

Correspondence to Hua Han or Ying-Min Liang.

Additional information

Guo-Hui Li, Yu-Zhen Fan, Xiao-Wei Liu, Bing-Fang Zhang contributed equally to this study.

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Li, GH., Fan, YZ., Liu, XW. et al. Notch signaling maintains proliferation and survival of the HL60 human promyelocytic leukemia cell line and promotes the phosphorylation of the Rb protein. Mol Cell Biochem 340, 7–14 (2010). https://doi.org/10.1007/s11010-010-0394-9

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  • DOI: https://doi.org/10.1007/s11010-010-0394-9

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