title: fps/fes knockout mice display a lactation defect and the fps/fes tyrosine kinase is a component of E-cadherin-based adherens junctions in breast epithelial cells during lactation.
abstract: The fps/fes proto-oncogene encodes a cytoplasmic protein-tyrosine kinase implicated in vesicular trafficking and cytokine and growth factor signaling in hematopoietic, neuronal, vascular endothelial and epithelial lineages. Genetic evidence has suggested a tumor suppressor role for Fps/Fes in breast and colon. Here we used fps/fes knockout mice to investigate potential roles for this kinase in development and function of the mammary gland. Fps/Fes expression was induced during pregnancy and lactation, and its kinase activity was dramatically enhanced. Milk protein and fat composition from nursing fps/fes-null mothers was normal; however, pups reared by them gained weight more slowly than pups reared by wild-type mothers. Fps/Fes displayed a predominantly dispersed punctate intracellular distribution which was consistent with vesicles within the luminal epithelial cells of lactating breast, while a small fraction co-localized with beta-catenin and E-cadherin on their basolateral surfaces. Fps/Fes was found to be a component of the E-cadherin adherens junction (AJ) complex; however, the phosphotyrosine status of beta-catenin and core AJ components in fps/fes-null breast tissue was unaltered, and epithelial cell AJs and gland morphology were intact. We conclude that Fps/Fes is not essential for the maintenance of epithelial cell AJs in the lactating breast but may instead play important roles in vesicular trafficking and milk secretion.
authors.affiliation: Division of Cancer Biology and Genetics, Queen's University Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Truesdell
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Zirngibl
authors.forename: Sarah
authors.initials: S
authors.lastname: Francis
authors.forename: Waheed
authors.initials: W
authors.lastname: Sangrar
authors.forename: Peter A
authors.initials: PA
authors.lastname: Greer
mesh_terms: D000818:Animals; D015820:Cadherins / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D015151:Immunoblotting; D007774:Lactation / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008892:Milk / Q000378:metabolism; D008894:Milk Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051578:Proto-Oncogene Proteins c-fes / Q000172:deficiency* / Q000235:genetics
chemical_list: D015820:Cadherins; D008894:Milk Proteins; D011505:Protein-Tyrosine Kinases; C496646:Fes protein, mouse; D051578:Proto-Oncogene Proteins c-fes