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Molecular and Cellular Biology, February 2002, p. 1060-1072, Vol. 22, No. 4
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.4.1060-1072.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Activation of NF-{kappa}B Is Essential for Hepatocyte Growth Factor-Mediated Proliferation and Tubulogenesis{dagger}

Markus Müller,,{ddagger} Alessandro Morotti, and Carola Ponzetto*

Department of Anatomy and Pharmacology, University of Turin, 10126 Turin, Italy

Received 16 April 2001/ Returned for modification 30 May 2001/ Accepted 26 November 2001

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-{kappa}B 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-{kappa}B in HGF/Met signaling. HGF stimulates NF-{kappa}B DNA binding and transcriptional activation via the canonical I{kappa}B 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-{kappa}B activation. Blockage of NF-{kappa}B activation in MLP29 cells by forced expression of the NF-{kappa}B super-repressor I{kappa}B{alpha}2A does not interfere with HGF-induced scatter but inhibits proliferation and tubulogenesis. Surprisingly, in the same cells NF-{kappa}B appears to be dispensable for the antiapoptotic function of HGF.

* Corresponding author. Mailing address: Dept. of Anatomy, Pharmacology and Forensic Medicine, C.so Massimo d'Azeglio 52, 10126 Turin, Italy. Phone: 39-011-670 7799. Fax: 39-011-670 7732. E-mail: carola.ponzetto{at}unito.it.

{dagger} This work is dedicated to the memory of Franco Tatò, who died on 7 July 2001.

{ddagger} EMBL, Monterotondo-Scalo, 00016 Rome, Italy.

Molecular and Cellular Biology, February 2002, p. 1060-1072, Vol. 22, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.4.1060-1072.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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