Effect of PDK1 on Notch1-Induced Mouse T-cell Acute Lymphoblastic Leukemia / 中国实验血液学杂志
Journal of Experimental Hematology
;
(6): 637-642, 2016.
Article
in Chinese
| WPRIM
| ID: wpr-360033
ABSTRACT
<p><b>OBJECTIVE</b>To explore the role of PDK1 in T-ALL development through establishing the Notch1-induced T-ALL mouse model by using Mx1-cre; LoxP system to knock-out PDK1.</p><p><b>METHODS</b>Cell cycle and apoptosis of leukemic cells were detected by flow cytometry, and relative expression of tumor-related genes and transcription factors of leukemic cells were determined by quantitative real-time PCR.</p><p><b>RESULTS</b>Notch1-induced T-ALL mouse model with inducible knock-out of PDK1 was established successfully. Compared to T-ALL control mouse model, PDK1 knock-out mice showed a significant longer survival time (P<0.01). There was no difference of cell cycle between control and PDK1 knock-out mice, and the apoptosis rate of leukemic cells in PDK1 knock-out mice was higher than that of control mice (P<0.001). PDK1 knock-out resulted in decreased expression of tumor-related genes and transcription factors, such as c-Myc and NF-κB (P<0.01), and increased expression level of P53 (P<0.01).</p><p><b>CONCLUSION</b>PDK1 knock-out can inhibit the development of T-ALL, and its mechanism may be the leukemia progression inhibited by regulating the apoptosis and expression of multiple related genes and transcription factors.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Gene Expression Regulation, Leukemic
/
Cell Cycle
/
NF-kappa B
/
Tumor Suppressor Protein p53
/
Proto-Oncogene Proteins c-myc
/
Protein Serine-Threonine Kinases
/
Apoptosis
/
Mice, Knockout
/
Disease Models, Animal
/
Receptor, Notch1
Type of study:
Prognostic study
Limits:
Animals
Language:
Chinese
Journal:
Journal of Experimental Hematology
Year:
2016
Type:
Article
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