Differential expression of Csk homologous kinase (CHK) in normal brain and brain tumors.
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.
Kim
Sun-Ok
SO
AgroPharma Research Institute, Dongbu Hannong Chemical Co, Taejon, South Korea.
Avraham
Shalom
S
Jiang
Shuxian
S
Zagozdzon
Radoslaw
R
Fu
Yigong
Y
Avraham
Hava Karsenty
HK
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D000081247:CSK Tyrosine-Protein Kinase; D002454:Cell Differentiation; D002455:Cell Division; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
D009419:Nerve Tissue Proteins; D020320:Oligoribonucleotides, Antisense; C091243:Matk protein, rat; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C085377:MATK protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases; C000631346:CSK protein, human