title: Decreased expression of beta1-integrin and focal adhesion kinase in epithelial cells may initiate involution of mammary glands.
abstract: The mechanisms regulating involution of mammary glands after weaning are not clear, but engorgement with milk is a key trigger. Many cell types require to be anchored to an extracellular matrix (ECM) as a prerequisite for survival and this is achieved via intregrins binding to specific motifs and signalling their attachment, intracellularly, via focal adhesion kinase (FAK). We sought to determine firstly, if expression of beta1-integrin and FAK is reduced during the first stage of involution. Expression of beta1-integrin and FAK was significantly reduced at 6 h after sealing teats and this was accompanied with a decreased abundance of cytochrome C in mitochondria. Secondly, we sought to determine if expression of beta1-integrin and FAK was restored during the first, partially reversible stage of involution (at 24 h), but not during the second irreversible stage, which occurs after 72 h. Re-suckling restored full expression of the 80 kDa fragment of FAK, but not of the 125 kDa protein or beta1-integrin at 24 h after weaning. Re-suckling did not restore expression of either peptide after 72 h. Changes in expression of cytochrome C and pro-caspase-3 (apoptotic markers) were similar to that of the 80 kDa fragment of FAK. These data suggest that epithelial cells can restore partial contact with their basement membrane during the first, reversible stage, but not during the second irreversible stage of involution. We speculate that decreased contact between epithelial cells and their basement membrane initiates apoptosis in mammary glands at weaning. This process begins within 6 h of pup withdrawal.
authors.affiliation: Dairy Biotechnology Group, AgResearch Ltd., Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand. chris.mcmahon@agresearch.co.nz
authors.forename: Christopher D
authors.initials: CD
authors.lastname: McMahon
authors.forename: Vicki C
authors.initials: VC
authors.lastname: Farr
authors.forename: Kuljeet
authors.initials: K
authors.lastname: Singh
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Wheeler
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Davis
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D045304:Cytochromes c / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D007774:Lactation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D008928:Mitochondria / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019012:Integrin beta1; D045304:Cytochromes c; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases