Phenotype-assisted transcriptome analysis identifies FOXM1 downstream from Ras-MKK3-p38 to regulate in vitro cellular invasion
A Behren, S Muehlen, GA Acuna Sanhueza, C Schwager, PK Plinkert, PE Huber, A Abdollahi, C Simon
ONCOGENE | NATURE PUBLISHING GROUP | Published : 2010
The Ras oncogene is known to activate three major MAPK pathways, ERK, JNK, p38 and exert distinct cellular phenotypes, that is, apoptosis and invasion through the Ras-MKK3-p38-signaling cascade. We attempted to identify the molecular targets of this pathway that selectively govern the invasive phenotype. Stable transfection of NIH3T3 fibroblasts with MKK3(act) cDNA construct revealed similar p38-dependent in vitro characteristics observed in Ha-Ras(EJ)-transformed NIH3T3 cells, including enhanced invasiveness and anchorage-independent growth correlating with p38 phosphorylation status. To identify the consensus downstream targets of the Ras-MKK3-p38 cascade involved in invasion, in vitro inv..View full abstract
Awarded by German Krebshilfe (Deutsche Krebshilfe)
Awarded by NSCOR
Awarded by DFG
We thank Thomas Regiert (DKFZ) for excellent technical assistance with microarray analysis. We also thank J Han (Scripps Research Institute) for providing us with the MKK3(b) expression construct and RH Medema (Laboratory of Experimental Oncology, University Medical Center Utrecht) for the FoxM1 promoter construct. This work was supported by the German Krebshilfe (Deutsche Krebshilfe, 107691, to CS, PH, PP and AA), NSCOR NNJ04HJ12G and DFG-SPP1190 (to AA and PH) and DFG-Si634-5/1 (to CS and PP).