title: Mammary epithelial-specific deletion of the focal adhesion kinase gene leads to severe lobulo-alveolar hypoplasia and secretory immaturity of the murine mammary gland.
abstract: Integrin-mediated cell adhesion and signaling is required for mammary gland development and functions. As a major mediator of integrin signaling, focal adhesion kinase (FAK) has been implicated to play a role in the survival, proliferation, and differentiation of mammary epithelial cells in previously studies in vitro. To assess the role of FAK in vivo, we created mice in which FAK is selectively deleted in mammary epithelial cells. The mammary gland FAK conditional knock-out (MFCKO) mice are viable, fertile, and macroscopically indistinguishable from the control littermates. In virgin MFCKO mice, mammary ductal elongation is retarded at 5 weeks of age but reaches the full extent by 8 weeks of age compared with the control mice. However, the MFCKO females are unable to nurse their pups due to severe lobulo-alveolar hypoplasia and secretory immaturity during pregnancy and lactation. Analysis of the mammary epithelial cells in MFCKO mice showed reduced Erk phosphorylation, expression of cyclin D1, and a corresponding decrease in proliferative capability compared with the littermate controls. In addition, phosphorylation of STAT5 and expression of whey acidic protein are significantly reduced in the mammary glands of MFCKO mice, suggesting defective secretory maturation in these mice. Therefore, the combination of the severe lobulo-alveolar hypoplasia and defective secretory differentiation is responsible for the inability of the MFCKO females to nurse their pups. Together, these results provide strong support for a role of FAK in the mammary gland development and function in vivo.
authors: Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA.
authors: Tamas
authors: T
authors: Nagy
authors: Huijun
authors: H
authors: Wei
authors: Tang-Long
authors: TL
authors: Shen
authors: Xu
authors: X
authors: Peng
authors: Chun-Chi
authors: CC
authors: Liang
authors: Boyi
authors: B
authors: Gan
authors: Jun-Lin
authors: JL
authors: Guan
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics*; D017353:Gene Deletion; D007774:Lactation / Q000235:genetics / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D050799:STAT5 Transcription Factor / Q000378:metabolism
chemical_list: D056741:Cyclin D; D016213:Cyclins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C024471:whey acidic proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases