Hepatocyte growth factor (HGF) and its receptor, Met, regulate a number of biological functions in epithelial and nonepithelial cells, such as survival, motility, proliferation, and tubular morphogenesis. The transcription factor NF-kappaB is activated in response to a wide variety of stimuli, including growth factors, and is involved in biological responses in part overlapping with those triggered by HGF. In this work we used the liver-derived MLP29 cell line to study the possible involvement of NF-kappaB in HGF/Met signaling. HGF stimulates NF-kappaB DNA binding and transcriptional activation via the canonical IkappaB phosphorylation-degradation cycle and via the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase cascades. Phosphatidylinositol 3-kinase is not involved in Met-mediated NF-kappaB activation. Blockage of NF-kappaB activation in MLP29 cells by forced expression of the NF-kappaB super-repressor IkappaB(alpha)2A does not interfere with HGF-induced scatter but inhibits proliferation and tubulogenesis. Surprisingly, in the same cells NF-kappaB appears to be dispensable for the antiapoptotic function of HGF.

Activation of NF-kappaB is essential for hepatocyte growth factor-mediated proliferation and tubulogenesis.

MOROTTI, Alessandro;PONZETTO, Carola
2002-01-01

Abstract

Hepatocyte growth factor (HGF) and its receptor, Met, regulate a number of biological functions in epithelial and nonepithelial cells, such as survival, motility, proliferation, and tubular morphogenesis. The transcription factor NF-kappaB is activated in response to a wide variety of stimuli, including growth factors, and is involved in biological responses in part overlapping with those triggered by HGF. In this work we used the liver-derived MLP29 cell line to study the possible involvement of NF-kappaB in HGF/Met signaling. HGF stimulates NF-kappaB DNA binding and transcriptional activation via the canonical IkappaB phosphorylation-degradation cycle and via the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase cascades. Phosphatidylinositol 3-kinase is not involved in Met-mediated NF-kappaB activation. Blockage of NF-kappaB activation in MLP29 cells by forced expression of the NF-kappaB super-repressor IkappaB(alpha)2A does not interfere with HGF-induced scatter but inhibits proliferation and tubulogenesis. Surprisingly, in the same cells NF-kappaB appears to be dispensable for the antiapoptotic function of HGF.
2002
22
1060
1072
MULLER M.; MOROTTI A.; C. PONZETTO
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/37381
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