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Inverse regulation of bridging integrator 1 and BCR-ABL1 in chronic myeloid leukemia
- Source :
- Tumor Biology. 37:217-225
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Endocytosis is the major regulator process of tyrosine kinase receptor (RTK) functional activities. Bridging integrator 1 (BIN1) is a key protein involved in RTK intracellular trafficking. Here, we report, by studying 34 patients with chronic myeloid leukemia (CML) at diagnosis, that BIN1 gene is downregulated in CML as compared to healthy controls, suggesting an altered endocytosis of RTKs. Rab interactor 1 (RIN1), an activator of BIN1, displayed a similar behavior. Treatment of 57 patients by tyrosine kinase inhibitors caused, along with BCR-ABL1 inactivation, an increase of BIN1 and RIN1 expression, potentially restoring endocytosis. There was a significant inverse correlation between BIN1-RIN1 and BCR-ABL1 expression. In vitro experiments on both CML and nontumorigenic cell lines treated with Imatinib confirmed these results. In order to provide another proof in favor of BIN1 and RIN1 endocytosis function in CML, we demonstrated that Imatinib induced, in K562 cell line, BIN1-RIN1 upregulation accompanied by a parallel AXL receptor internalization into cytoplasmic compartment. This study shows a novel deregulated mechanism in CML patients, indicating BIN1 and RIN1 as players in the maintenance of the abnormal RTK signaling in this hematological disease.
- Subjects :
- 0301 basic medicine
Cytoplasm
Cancer Research
Bridging integrator 1
Fusion Proteins, bcr-abl
Bone Marrow Cells
Real-Time Polymerase Chain Reaction
Endocytosis
Receptor tyrosine kinase
03 medical and health sciences
Downregulation and upregulation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Proto-Oncogene Proteins
hemic and lymphatic diseases
medicine
Humans
AXL
BCR-ABL1
Chronic myeloid leukemia
Rab interactor 1
Adaptor Proteins, Signal Transducing
biology
Gene Expression Regulation, Leukemic
Gene Expression Profiling
Tumor Suppressor Proteins
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Receptor Protein-Tyrosine Kinases
Myeloid leukemia
Imatinib
General Medicine
Axl Receptor Tyrosine Kinase
Up-Regulation
Cell biology
Gene Expression Regulation, Neoplastic
HEK293 Cells
030104 developmental biology
Drug Resistance, Neoplasm
Leukocytes, Mononuclear
biology.protein
Cancer research
Rab
K562 Cells
Tyrosine kinase
Signal Transduction
medicine.drug
K562 cells
Subjects
Details
- ISSN :
- 14230380 and 10104283
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Tumor Biology
- Accession number :
- edsair.doi.dedup.....ac24285c3bb2bda01af8ed7d2b1d1018