Transcriptional activation of the mouse Necl-5/Tage4/PVR/CD155 gene by fibroblast growth factor or oncogenic Ras through the Raf-MEK-ERK-AP-1 pathway.
Necl-5/Tage4/poliovirus receptor/CD155 is the poliovirus receptor and upregulated in rodent and human carcinoma. We have recently shown that mouse Necl-5 is upregulated by an oncogenic Ki-Ras (V12Ki-Ras) in NIH3T3 cells and enhances cell movement induced by growth factors, including platelet-derived growth factor and fibroblast growth factor (FGF), in an integrin alpha(v)beta(3)-dependent manner in wild type and V12Ki-Ras-transformed NIH3T3 cells. In addition, it enhances the growth factor-induced cell proliferation. We examined here how mouse Necl-5 was upregulated by V12Ki-Ras in NIH3T3 cells. Expression of the luciferase reporter gene fused to the Necl-5 promoter was induced by V12Ki-Ras in NIH3T3 cells. This induction was mediated through the Raf-MEK-ERK pathway. The Necl-5 promoter has an AP-1-binding site and this site was required for the V12Ki-Ras-induced activation of the Necl-5 promoter. Expression of the luciferase reporter gene fused to the Necl-5 promoter was also induced by FGF through the Raf-MEK-ERK-AP-1 pathway in NIH3T3 cells. These results indicate that the expression of mouse Necl-5 is induced by FGF or V12Ki-Ras through the Raf-MEK-ERK-AP-1 pathway.
Hirota
Takeshi
T
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
Irie
Kenji
K
Okamoto
Ryoko
R
Ikeda
Wataru
W
Takai
Yoshimi
Y
D016475:3T3 Cells; D000818:Animals; D000951:Antigens, Neoplasm / Q000187:drug effects / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000235:genetics*; D017931:DNA Primers; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D011905:Genes, ras; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D048490:raf Kinases / Q000378:metabolism*
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C476587:Taa1 protein, mouse; D018808:Transcription Factor AP-1; D005346:Fibroblast Growth Factors; D048490:raf Kinases