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 |
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Authors: | Peter F Truesdell Ralph A Zirngibl Waheed Sangrar Peter A Greer |
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Institution: | a Division of Cancer Biology and Genetics, Queen's University Cancer Research Institute, Queen's University, Kingston, Ontario, Canada K7L-3N6 b Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada K7L-3N6 |
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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 β-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 β-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. |
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Keywords: | AJ adherens junction F-BAR FCH-containing BIN/Amphiphysin/Rvs SH2 Src homology-2 TLR4 Toll-like receptor 4 FBS fetal bovine serum BSA bovine serum albumin EGF epidermal growth factor SMA smooth muscle actin FITC fluorescein isothiocyanate PBS phosphate buffered saline DMEM Dulbecco's modified Eagle's medium IP immunoprecipitation IB immunoblot |
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