期刊
EMBO JOURNAL
卷 30, 期 10, 页码 1896-1906出版社
WILEY
DOI: 10.1038/emboj.2011.113
关键词
contraction; integrin; mammary gland; myoepithelium; Rho-GTPases
资金
- La Ligue Nationale Contre le Cancer
- Agence Nationale de la Recherche [ANR-08-BLAN-0078-01]
- La Fondation pour la Recherche Medicale
- Institut National du Cancer
- Canceropole Ile de France
- Agence Nationale de la Recherche (ANR) [ANR-08-BLAN-0078] Funding Source: Agence Nationale de la Recherche (ANR)
In the functionally differentiated mammary gland, basal myoepithelial cells contract to eject the milk produced by luminal epithelial cells from the body. We report that conditional deletion of a laminin receptor, alpha 3 beta 1 integrin, from myoepithelial cells leads to low rates of milk ejection due to a contractility defect but does not interfere with the integrity or functional differentiation of the mammary epithelium. In lactating mammary gland, in the absence of alpha 3 beta 1, focal adhesion kinase phosphorylation is impaired, the Rho/Rac balance is altered and myosin light-chain (MLC) phosphorylation is sustained. Cultured mammary myoepithelial cells depleted of alpha 3 beta 1 contract in response to oxytocin, but are unable to maintain the state of post-contractile relaxation. The expression of constitutively active Rac or its effector p21-activated kinase (PAK), or treatment with MLC kinase (MLCK) inhibitor, rescues the relaxation capacity of mutant cells, strongly suggesting that alpha 3 beta 1-mediated stimulation of the Rac/PAK pathway is required for the inhibition of MLCK activity, permitting completion of the myoepithelial cell contraction/relaxation cycle and successful lactation. This is the first study highlighting the impact of alpha 3 beta 1 integrin signalling on mammary gland function. The EMBO Journal (2011) 30, 1896-1906. doi: 10.1038/emboj.2011.113; Published online 12 April 2011
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