E-GEOD-7342 - Transcription profiling of mouse embryonic day 13.5 and 15.5 fetal livers lacking p38alpha, a mitogen-activated kinase that controls inflammatory responses and cell proliferation
Released on 13 December 2007, last updated on 30 April 2015
The mitogen-activated protein kinase (MAPK) p38alpha controls inflammatory responses and cell proliferation. Using mice carrying conditional p38alpha alleles, we investigated its function in postnatal development and tumorigenesis. When p38alpha is specifically deleted in the mouse embryo, fetuses develop to term but die shortly after birth, likely due to lung dysfunction. Fetal hematopoietic cells and embryonic fibroblasts deficient in p38alpha display increased proliferation, resulting from sustained activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway. Importantly, in chemical-induced liver cancer development, mice with liver-specific deletion of p38alpha show enhanced hepatocyte proliferation and tumor development that also correlates with JNK/c-Jun upregulation. Furthermore, increased proliferation of p38alpha-deficient hepatocytes and tumor cells is suppressed by inactivation of JNK or c-Jun. These results reveal a novel mechanism whereby p38alpha negatively regulates cell proliferation through antagonizing the JNK/c-Jun pathway in multiple cell types and in liver cancer development. We used microarrays to identifiy differental regulated genes by p38alpha in fetal liver cells Experiment Overall Design: Wild type and p38 deficient fetal liver cell were used for RNA extraction and hybridization on Affymetrix microarrays.
transcription profiling by array, co-expression, development or differentiation, individual genetic characteristics
p38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway. Lijian Hui, Latifa Bakiri, Andreas Mairhorfer, Norbert Schweifer, Christian Haslinger, Lukas Kenner, Vukoslav Komnenovic, Harald Scheuch, Hartmut Beug, Erwin F Wagner.