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Neoplasma Vol.54, p.503-510, 2007 |
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Title: JNK2 and p38 MAPK over-expressions do not represent key events in chronic myeloid leukemia transformation | ||
Author: M. MERKEROVA, H. BRUCHOVA, R. BRDICKA | ||
Abstract: Over-expression of two members of MAP kinase family (JNK2 and p38) has been already observed in chronic myeloid
leukemia (CML). In the present study, significance of this deregulation was investigated. Impacts of JNK2/p38 suppression
on gene expression profile of CML cell lines (K562/KU-812) were studied using an experimental approach that combines
siRNA-mediated specific inhibition of the genes and array-based expression analyses. After JNK2 depletion, 27 out of 588
tested genes showed significant expression changes, with 13 down-regulated genes and 14 up-regulated genes. Among
others, expression of MSH2 and MSH6, mdm2, and caspase-2 was reduced and, on the other hand, MKK1 and MKK6,
RFC2, cytokeratins K18 and K19, BAD, and DR5 expression was up-regulated. In the case of p38 silencing, 20 genes were
considered as significantly deregulated (7 genes reduced, 13 over-expressed). These genes included caspase-10, SOD1, and
Notch4 (down-regulation) and caspase-2 and caspase-3, CDC2, CDK4, and c-kit (up-regulation). In conclusion, comparison
of expression profiles after JNK2 or p38 gene silencing revealed distinct sets of affected genes. The results implied an
unequal impact of the MAPK deregulation on the CML cells. Further, we demonstrated that neither JNK2 nor p38 siRNAmediated
inhibition led to significant change of CML cell proliferation. It suggests that there are other important, likely upstream
regulators essential for CML malignant cell growth/transformation; therefore, separate inhibition of JNK2 or p38
MAPK gene is not sufficient for a proliferation arrest. |
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Keywords: expression arrays; JNK2; MAPK; p38; siRNA | ||
Year: 2007, Volume: 54, Issue: | Page From: 503, Page To: 510 | |
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