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CIP2A is overexpressed and involved in the pathogenesis of chronic myelocytic leukemia by interacting with breakpoint cluster region-Abelson leukemia virus
- Source :
- Medical Oncology. 31
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- To detect the expression of cancerous inhibitor of phosphatase 2A (CIP2A) in chronic myelocytic leukemia (CML) and investigate the mechanism underlying CIP2A knockdown-mediated cell proliferation and apoptosis as well as the interaction of CIP2A with breakpoint cluster region-Abelson leukemia virus (BCR-ABL). CIP2A mRNA and protein expression in chronic myelocytic leukemia-chronic (CML-CP) patients and healthy controls were determined by RT-PCR and Western blot. In vivo, c-Myc expression, PP2A activity, cell proliferation, and apoptosis of CML cells were detected with CIP2A depletion. In addition, the relationship among CIP2A, BCR-ABL, and tyrosine phosphatase SHP-1 was explored by depleting/overexpressing CIP2A or inhibiting BCR-ABL. The level of CIP2A mRNA was higher in CML-CP patients than healthy controls (56/74, 75.7 % vs. 1/35, 2.9 %, P < 0.001), and CIP2A protein was overexpressed in corresponding specimens. CIP2A knockdown by siRNA reduced the level of c-Myc protein and clonogenic formation, inhibited the activity of PP2A, K562 cell proliferation, and promoted cell apoptosis. Suppressing BCR-ABL by imatinib mesylate (IM) significantly decreased CIP2A expression. CIP2A knockdown decreased BCR-ABL but increased SHP-1 expression, and CIP2A overexpression had the reverse effect. CIP2A is overexpressed in CML-CP patients, and its expression may promote CML pathogenesis. CIP2A and BCR-ABL can regulate each other in a positive feedback loop. CIP2A may be a useful therapeutic target in CML-CP, particularly in patients with IM resistance. However, further studies are needed to validate the interaction between CIP2A and BCR-ABL using other tyrosine kinase inhibitors than IM.
- Subjects :
- Adult
Male
Cancer Research
Fusion Proteins, bcr-abl
Apoptosis
Protein tyrosine phosphatase
Biology
Autoantigens
Piperazines
Proto-Oncogene Proteins c-myc
Young Adult
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
hemic and lymphatic diseases
medicine
Humans
neoplasms
Aged
Cell Proliferation
Gene knockdown
Gene Expression Regulation, Leukemic
Intracellular Signaling Peptides and Proteins
breakpoint cluster region
Membrane Proteins
Hematology
General Medicine
Abelson leukemia virus
Middle Aged
medicine.disease
Molecular biology
Leukemia
Pyrimidines
Imatinib mesylate
Oncology
Case-Control Studies
Gene Knockdown Techniques
Benzamides
Imatinib Mesylate
Female
K562 Cells
Tyrosine kinase
K562 cells
Subjects
Details
- ISSN :
- 1559131X and 13570560
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Medical Oncology
- Accession number :
- edsair.doi.dedup.....aedd10c8ba198906cb97c2e70d7556dd