We are upgrading the repository! A content freeze is in effect until December 6, 2024. New submissions or changes to existing items will not be allowed during this period. All content already published will remain publicly available for searching and downloading. Updates will be posted in the Website Upgrade 2024 FAQ in the sidebar Help menu. Reach out to escholarship@umassmed.edu with any questions.
Integrin beta4 regulation of PTHrP underlies its contribution to mammary gland development
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
UMass Chan Affiliations
Department of Molecular, Cell and Cancer BiologyDocument Type
Journal ArticlePublication Date
2015-11-15Keywords
Developmental Biology
Metadata
Show full item recordAbstract
The integrin alpha6beta4 (referred to as beta4) is expressed in epithelial cells where it functions as a laminin receptor. Although in vitro studies have implicated beta4 in the biology of mammary epithelial cells, its contribution to mammary gland development has not been settled. To address this problem, we generated and analyzed itgb4(flox/flox)MMTV-Cre(-) and itgb4(flox/flox)MMTV-Cre(+) mice. The salient features of embryonic mammary tissue from itgb4(flox/flox)MMTV-Cre(+) mice were significantly smaller mammary buds and increased apoptosis in the surrounding mesenchyme. Also, compared to control glands, the itgb4-deleted mammary buds lacked expression of the progenitor cell marker CK14 and they were unable to generate mammary glands upon transplantation into cleared fat pads of recipient mice. Analysis of mammary glands at puberty and during pregnancy revealed that itgb4-diminished mammary tissue was unable to elongate and undergo branching morphogenesis. Micro-dissection of epithelial cells in the mammary bud and of the surrounding mesenchyme revealed that loss of beta4 resulted in a significant decrease in the expression of parathyroid hormone related protein (PTHrP) in epithelial cells and of target genes of the PTHrP receptor in mesenchymal cells. Given that the phenotype of the itgb4-deleted mammary tissue mimicked that of the PTHrP knockout, we hypothesized that beta4 contributes to mammary gland development by sustaining PTHrP expression and enabling PTHrP signaling. Indeed, the inability of itgb4-deleted mammary buds to elongate was rescued by exogenous PTHrP. These data implicate a critical role for the beta4 integrin in mammary gland development and provide a mechanism for this role.Source
Dev Biol. 2015 Nov 15;407(2):313-20. doi: 10.1016/j.ydbio.2015.09.015. Epub 2015 Sep 30. Link to article on publisher's siteDOI
10.1016/j.ydbio.2015.09.015Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36554PubMed ID
26432258Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.ydbio.2015.09.015