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Differential expression of Csk homologous kinase (CHK) in normal brain and brain tumors
Sun-Ok Kim1, Shalom Avraham, Shuxian Jiang
1AgroPharma Research Institute, Dongbu Hannong Chemical Co, Taejon, South Korea.
Background:
Substantial evidence supports the suggestion that carboxyl-terminal Src kinase (Csk) and Csk homologous kinase (CHK), two negative regulatory kinases of the Src tyrosine kinase family, play distinct roles during development of the central nervous system (CNS).
Methods:
To further examine the individual roles of CHK and Csk in the CNS, the authors compared the expression patterns of Csk and CHK during differentiation of primary hippocampal neurons.
Results:
Opposite patterns of expression were observed for CHK and Csk. The authors observed an increase in CHK expression and a decline in Csk expression during differentiation of primary hippocampal neurons, but no difference in Src expression levels. CHK was also expressed in astrocytes and oligodendrocytes in a differentiation-dependent manner. However, CHK expression was not detected in brain endothelial cells, transformed neuroblastoma or astrocytoma cell lines, nor in primary human neuroblastoma and glioblastoma tumors (10 cases), indicating that loss of CHK expression is associated with human brain tumors. Treatment with antisense CHK oligodeoxynucleotides blocked the neuronal process formation of primary hippocampal neurons and neuronal differentiation of PC12 cells. CHK overexpression in primary hippocampal neurons using recombinant adenovirus infection resulted both in increased CHK kinase activity and changes in neuronal morphology. In addition, CHK overexpression in neuroblastoma and astrocytoma cells inhibited their growth and proliferation.
Conclusions:
These findings strongly suggested that CHK may play a role in tumorigenesis and in the terminal differentiation of neurons within the CNS.
Insights
Csk homologous kinase (CHK) plays a key role in central nervous system (CNS) development and neuronal differentiation. Loss of CHK expression is linked to human brain tumors, suggesting CHK involvement in tumorigenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- Carboxyl-terminal Src kinase (Csk) and Csk homologous kinase (CHK) are negative regulators of Src tyrosine kinases.
- These kinases are implicated in distinct roles during central nervous system (CNS) development.
Purpose of the Study:
- To investigate the individual roles of CHK and Csk in the CNS.
- To compare the expression patterns of Csk and CHK during primary hippocampal neuron differentiation.
Main Methods:
- Compared Csk and CHK expression during primary hippocampal neuron differentiation.
- Assessed CHK expression in various brain cell types and human tumors.
- Utilized antisense CHK oligodeoxynucleotides and recombinant adenovirus for functional studies.
- Examined the effect of CHK modulation on neuronal differentiation and cell proliferation.
Main Results:
- Observed inverse expression patterns: CHK increased, Csk decreased during neuronal differentiation.
- Found CHK expression in astrocytes and oligodendrocytes, but not in brain endothelial cells or tumor cell lines.
- Loss of CHK expression correlated with human brain tumors.
- Antisense CHK inhibited neuronal process formation and differentiation.
- CHK overexpression altered neuronal morphology and inhibited tumor cell growth.
Conclusions:
- Findings suggest CHK is involved in neuronal terminal differentiation within the CNS.
- Results indicate a potential role for CHK in tumorigenesis.
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