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| Subject Categories: Cell & Tissue Architecture | Development |
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| The EMBO Journal
(2005) 24, 1942–1953, doi:10.1038/sj.emboj.7600674 Published online 12 May 2005 |
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 1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli |
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| Na Li1, Yu Zhang1, Matthew J Naylor2, Franziska Schatzmann2, Francisca Maurer1, Tim Wintermantel3, Gunther Schuetz3, Ulrich Mueller4, Charles H Streuli2 and Nancy E Hynes1 |
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1 Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland 2 Faculty of Life Sciences, University of Manchester, Manchester, UK 3 Division Molecular Biology of the Cell I, German Cancer Center, Heidelberg, Germany 4 The Scripps Research Institute, Department of Cell Biology, LaJolla, CA, USA To whom correspondence should be addressed 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; Published online 12 May 2005. |
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| Abstract |
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| 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. |
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| Keywords: 1 integrin, focal adhesion kinase, mammary gland, MDA-MB-231 breast cancer cells, p21Cip1 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHModulation of glomerular hypertension defines susceptibility to progressive glomerular injury Kidney International Original Article Perturbation of β1-integrin function alters the development of murine mammary gland The EMBO Journal Article (15 Apr 1998) p63 regulates an adhesion programme and cell survival in epithelial cells Nature Cell Biology Article (01 Jun 2006) |
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