Article abstract
Nature Genetics 39, 750 - 758 (2007)
Published online: 29 April 2007 | doi:10.1038/ng2037
p38
MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation
Juan José Ventura1, Stephan Tenbaum1,5, Eusebio Perdiguero1,4,5, Marion Huth2, Carmen Guerra1, Mariano Barbacid1, Manolis Pasparakis2,3 & Angel R Nebreda1
Abstract
Stem cell function is central for the maintenance of normal tissue homeostasis. Here we show that deletion of p38
mitogen-activated protein (MAP) kinase in adult mice results in increased proliferation and defective differentiation of lung stem and progenitor cells both in vivo and in vitro. We found that p38 positively regulates factors such as CCAAT/enhancer-binding protein that are required for lung cell differentiation. In addition, p38 controls self-renewal of the lung stem and progenitor cell population by inhibiting proliferation-inducing signals, most notably epidermal growth factor receptor. As a consequence, the inactivation of p38 leads to an immature and hyperproliferative lung epithelium that is highly sensitized to K-RasG12V-induced tumorigenesis. Our results indicate that by coordinating proliferation and differentiation signals in lung stem and progenitor cells, p38 has a key role in the regulation of lung cell renewal and tumorigenesis.
- CNIO (Spanish National Cancer Center), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
- European Molecular Biology Laboratory (EMBL) Mouse Biology Unit, via Ramarini 32, 00016 Monterotondo, Italy.
- Institute for Genetics, University of Cologne, Zulpicher Str. 47, 50674 Cologne, Germany.
- Current address: Center for Genomic Regulation (CRG), E08003 Barcelona, Spain.
- These authors contributed equally to this work.
Correspondence to: Angel R Nebreda1 e-mail: anebreda@cnio.es
Correspondence to: Juan José Ventura1 e-mail: jjventura@cnio.es
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