Article
- The EMBO Journal (2005) 24, 1942 - 1953
- doi:10.1038/sj.emboj.7600674
Published online: 12 May 2005
Subject Categories:
1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli
Na Li1, Yu Zhang1, Matthew J Naylor2, Franziska Schatzmann2, Francisca Maurer1, Tim Wintermantel3, Gunther Schuetz3, Ulrich Mueller4, Charles H Streuli2 and Nancy E Hynes1
- Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
- Faculty of Life Sciences, University of Manchester, Manchester, UK
- Division Molecular Biology of the Cell I, German Cancer Center, Heidelberg, Germany
- The Scripps Research Institute, Department of Cell Biology, LaJolla, CA, USA
Correspondence to:
Nancy E Hynes, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Tel.: +41 61 697 8107; Fax: +41 61 697 8102; E-mail: nancy.hynes@fmi.ch
Received 25 October 2004; Accepted 14 April 2005
Abstract
Integrin–extracellular matrix interactions play important roles in the coordinated integration of external and internal cues that are essential for proper development. To study the role of 
1 integrin in the mammary gland, Itg1flox/flox mice were crossed with WAPiCre transgenic mice, which led to specific ablation of 1 integrin in luminal alveolar epithelial cells. In the 1 integrin mutant mammary gland, individual alveoli were disorganized resulting from alterations in cell–basement membrane associations. Activity of focal adhesion kinase (FAK) was also decreased in mutant mammary glands. Luminal cell proliferation was strongly inhibited in 1 integrin mutant glands, which correlated with a specific increase of p21Cip1 expression. In a p21Cip1 null background, there was a partial rescue of BrdU incorporation, providing in vivo evidence linking p21Cip1 to the proliferative defect observed in 1 integrin mutant glands. A connection between p21Cip1 and 1 integrin as well as FAK was also established in primary mammary cells. These results point to the essential role of 1 integrin signaling in mammary epithelial cell proliferation.
Keywords:
- 1 integrin,
- focal adhesion kinase,
- mammary gland,
- MDA-MB-231 breast cancer cells,
- p21Cip1
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