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dc.contributor.authorSun, X.en
dc.contributor.authorRobertson, S.en
dc.contributor.authorIngman, W.en
dc.date.issued2013en
dc.identifier.citationCytokine (Online), 2013; 61(2):377-388en
dc.identifier.issn1096-0023en
dc.identifier.issn1043-4666en
dc.identifier.urihttp://hdl.handle.net/2440/78960-
dc.description.abstractTransforming growth factor beta1 (TGFB1) is a multi-functional cytokine that regulates cell proliferation, apoptosis and immune system responses. In the breast, the mammary epithelium is the primary source of TGFB1 and increased expression is associated with increased breast cancer risk. This study was conducted to investigate the roles of epithelial cell-derived TGFB1 in regulation of epithelial cell activity and macrophage phenotype in the mammary gland. Tgfb1 null mutant and wildtype mammary epithelium was transplanted into contra-lateral sides of the cleared mammary gland of TGFB1 replete scid mice. Transplanted tissue was analysed for markers of proliferation and apoptosis to determine the effect of Tgfb1 null mutation on epithelial cell turnover, and was analysed by immunohistochemistry to investigate the location, abundance and phenotype of macrophages. The number of proliferating and dying ductal epithelial cells, determined by BrdU and TUNEL, was increased by 35% and 3.3-fold respectively in mammary gland transplanted with Tgfb1 null epithelium compared to wildtype epithelium (p<0.05). Abundance of F4/80+ macrophages in between Tgfb1 null epithelial cells compared to wildtype epithelial cells was increased by 50%. The number of iNOS+ and CCR7+ cells in the stroma surrounding Tgfb1 null alveolar epithelium was increased by 78% and 2-fold respectively, and dendriform MHC class II+ cells within ductal epithelium were decreased by 30%. We conclude that epithelial cell-derived TGFB1 in the mammary gland has two functions: (1) regulation of cellular turnover of epithelial cells, and (2) regulation of local macrophage phenotype. These findings shed new light on the diversity of roles of TGFB1 in the mammary gland which are likely to impact on breast cancer risk.en
dc.description.statementofresponsibilityXuan Sun, Sarah A. Robertson, Wendy V. Ingmanen
dc.language.isoenen
dc.publisherAcademic Pressen
dc.rights© 2012 Elsevier Ltd. All rights reserved.en
dc.subjectTransforming growth factor beta1; Mammary gland; Macrophage; Epitheliumen
dc.titleRegulation of epithelial cell turnover and macrophage phenotype by epithelial cell-derived transforming growth factor beta1 in the mammary glanden
dc.typeJournal articleen
dc.identifier.rmid0020124758en
dc.identifier.doi10.1016/j.cyto.2012.12.002en
dc.identifier.pubid21650-
pubs.library.collectionObstetrics and Gynaecology publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidSun, X. [0000-0002-3051-1720]en
dc.identifier.orcidRobertson, S. [0000-0002-9967-0084]en
dc.identifier.orcidIngman, W. [0000-0003-3116-2902]en
Appears in Collections:Obstetrics and Gynaecology publications

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