Abstract P4-05-02: Conditional inactivation of the 25-hydroxyvitamin D-24-hydroxylase (Cyp24a1) in the mouse mammary epithelium alters mammary gland development

2017 ◽  
Author(s):  
L Sheng ◽  
AG Turner ◽  
GA Tarulli ◽  
K Barratt ◽  
R Kremer ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Mammary Epithelium ◽  
Hydroxyvitamin D ◽  
Conditional Inactivation ◽  
25 Hydroxyvitamin D ◽  
Gland Development ◽  
Mouse Mammary Epithelium

Targeting heparanase to the mammary epithelium enhances mammary gland development and promotes tumor growth and metastasis

2018 ◽  
Vol 65 ◽  
pp. 91-103 ◽  
Author(s):  
Ilanit Boyango ◽  
Uri Barash ◽  
Liat Fux ◽  
Inna Naroditsky ◽  
Neta Ilan ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Tumor Growth ◽  
Mammary Gland Development ◽  
Mammary Epithelium ◽  
Tumor Growth And Metastasis ◽  
Gland Development

scholarly journals Regulation of Mammary Gland Branching Morphogenesis by EphA2 Receptor Tyrosine Kinase

2009 ◽  
Vol 20 (10) ◽  
pp. 2572-2581 ◽  
Author(s):  
David Vaught ◽  
Jin Chen ◽  
Dana M. Brantley-Sieders
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Mammary Epithelium ◽  
Branching Morphogenesis ◽  
Mammary Epithelial ◽  
Mammary Tissue ◽  
Wild Type ◽  
Epithelial Proliferation ◽  
Positive Role ◽  
Gland Development

Eph receptor tyrosine kinases, including EphA2, are expressed in the mammary gland. However, their role in mammary gland development remains poorly understood. Using EphA2-deficient animals, we demonstrate for the first time that EphA2 receptor function is required for mammary epithelial growth and branching morphogenesis. Loss of EphA2 decreased penetration of mammary epithelium into fat pad, reduced epithelial proliferation, and inhibited epithelial branching. These defects appear to be intrinsic to loss of EphA2 in epithelium, as transplantation of EphA2-deficient mammary tissue into wild-type recipient stroma recapitulated these defects. In addition, HGF-induced mammary epithelial branching morphogenesis was significantly reduced in EphA2-deficient cells relative to wild-type cells, which correlated with elevated basal RhoA activity. Moreover, inhibition of ROCK kinase activity in EphA2-deficient mammary epithelium rescued branching defects in primary three-dimensional cultures. These results suggest that EphA2 receptor acts as a positive regulator in mammary gland development, functioning downstream of HGF to regulate branching through inhibition of RhoA. Together, these data demonstrate a positive role for EphA2 during normal mammary epithelial proliferation and branching morphogenesis.

scholarly journals Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium

2000 ◽  
Vol 113 (12) ◽  
pp. 2129-2138 ◽  
Author(s):  
S. Naylor ◽  
M.J. Smalley ◽  
D. Robertson ◽  
B.A. Gusterson ◽  
P.A. Edwards ◽  
...  
Keyword(s):  
Cell Culture ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Ectopic Expression ◽  
Mammary Epithelium ◽  
Mouse Mammary Gland ◽  
Normal Mammary Gland ◽  
Gland Development

Several Wnt genes are expressed in the postnatal mouse mammary gland and are thought to be involved in mammary gland development. Ectopic expression of Wnt-1, which is not normally expressed in the mammary gland, drives the formation of a pre-neoplastic hyperplasia. Cell culture-based assays have shown that Wnt-1 and some mammary-expressed Wnts transform C57MG cells. This has led to the suggestion that Wnt-1 functions as an oncogene through the inappropriate activation of developmental events that are normally controlled by the ‘transforming’ class of Wnts. In this study, Wnt-7b was expressed in vivo using recombinant retroviruses. Wnt-7b did not alter normal mammary gland development despite having similar effects to Wnt-1 in cell culture. We conclude that the in vitro classification of Wnts as ‘transforming’ does not correlate with the transformation in vivo. To facilitate the analysis of Wnt-expression, a lacZ-containing, bicistronic recombinant retrovirus was developed. Immunohistochemistry and electron microscopy identified retrovirally transduced myoepithelial and luminal epithelial cells in normal and hyperplastic tissues. The distribution of transduced cells in mammary outgrowths was consistent with current models of mammary stem cell identity.

scholarly journals Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Parisa Rabieifar ◽  
Ting Zhuang ◽  
Tânia D. F. Costa ◽  
Miao Zhao ◽  
Staffan Strömblad
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Mammary Epithelium ◽  
Small Gtpases ◽  
Normal Mammary Gland ◽  
Knock Out ◽  
Adult Mice ◽  
Gland Development

Abstract p21-activated kinases (PAKs) are serine/threonine kinases functioning as downstream effectors of the small GTPases Rac1 and Cdc42. Members of the PAK family are overexpressed in human breast cancer, but their role in mammary gland development is not fully explored. Here we examined the functional role of PAK4 in mammary gland development by creating a mouse model of MMTV-Cre driven conditional PAK4 gene depletion in the mammary gland. The PAK4 conditional knock-out mice were born healthy, with no observed developmental deficits. Mammary gland whole-mounts revealed no defects in ductal formation or elongation of the mammary tree through the fat pad. PAK4 gene depletion also did not alter proliferation and invasion of the mammary epithelium in young virgin mice. Moreover, adult mice gave birth to healthy pups with normal body weight upon weaning. This implies that MMTV-Cre induced gene depletion of PAK4 in mice does not impair normal mammary gland development and thereby provides an in vivo model that can be explored for examination of the potential function of PAK4 in breast cancer.

Integrins in Mammary Gland Development and Differentiation of Mammary Epithelium

2003 ◽  
Vol 8 (4) ◽  
pp. 383-394 ◽  
Author(s):  
Ilaria Taddei ◽  
Marisa M. Faraldo ◽  
Jérôme Teulière ◽  
Marie-Ange Deugnier ◽  
Jean Paul Thiery ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Mammary Epithelium ◽  
Development And Differentiation ◽  
Gland Development

scholarly journals Epithelial Xbp1 Is Required for Cellular Proliferation and Differentiation during Mammary Gland Development

2015 ◽  
Vol 35 (9) ◽  
pp. 1543-1556 ◽  
Author(s):  
Daisuke Hasegawa ◽  
Veronica Calvo ◽  
Alvaro Avivar-Valderas ◽  
Abigale Lade ◽  
Hsin-I Chou ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Cellular Proliferation ◽  
Prolactin Receptor ◽  
Mammary Epithelium ◽  
Branching Morphogenesis ◽  
Direct Function ◽  
Proliferation And Differentiation ◽  
The Unfolded Protein Response ◽  
Gland Development

Xbp1, a key mediator of the unfolded protein response (UPR), is activated by IRE1α-mediated splicing, which results in a frameshift to encode a protein with transcriptional activity. However, the direct function of Xbp1 in epithelial cells during mammary gland development is unknown. Here we report that the loss of Xbp1 in the mammary epithelium through targeted deletion leads to poor branching morphogenesis, impaired terminal end bud formation, and spontaneous stromal fibrosis during the adult virgin period. Additionally, epithelial Xbp1 deletion induces endoplasmic reticulum (ER) stress in the epithelium and dramatically inhibits epithelial proliferation and differentiation during lactation. The synthesis of milk and its major components, α/β-casein and whey acidic protein (WAP), is significantly reduced due to decreased prolactin receptor (Prlr) and ErbB4 expression in Xbp1-deficient mammary epithelium. Reduction of Prlr and ErbB4 expression and their diminished availability at the cell surface lead to reduced phosphorylated Stat5, an essential regulator of cell proliferation and differentiation during lactation. As a result, lactating mammary glands in these mice produce less milk protein, leading to poor pup growth and postnatal death. These findings suggest that the loss of Xbp1 induces a terminal UPR which blocks proliferation and differentiation during mammary gland development.

scholarly journals Effect of glycogen synthase kinase-3 inactivation on mouse mammary gland development and oncogenesis

2013 ◽  
Author(s):  
Joanna Dembowy ◽  
Hibret A Adissu ◽  
Jeff C Liu ◽  
Eldad Zacksenhaus ◽  
James Robert Woodgett
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Glycogen Synthase ◽  
Mammary Epithelium ◽  
Intraepithelial Neoplasia ◽  
Tumor Formation ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Normal Mammary Gland ◽  
Gland Development

Many components of Wnt/β-catenin signaling pathway have critical functions in mammary gland development and tumor formation, yet the contribution of glycogen synthase kinase-3 (GSK-3α and GSK-3β) to mammopoiesis and oncogenesis is unclear. Here, we report that WAP-Cre-mediated deletion of GSK-3 in the mammary epithelium results in activation of Wnt/β-catenin signaling and induces mammary intraepithelial neoplasia that progresses to squamous transdifferentiation and development of adenosquamous carcinomas at 6 months. To uncover possible β-catenin-independent activities of GSK-3, we generated mammary-specific knock-outs of GSK-3 and β-catenin. Squamous transdifferentiation of the mammary epithelium was largely attenuated, however mammary epithelial cells lost the ability to form mammospheres suggesting perturbation of stem cell properties unrelated to loss of β-catenin alone. At 10 months, adenocarcinomas that developed in glands lacking GSK-3 and β-catenin displayed elevated levels of γ-catenin/plakoglobin as well as activation of the Hedgehog and Notch pathways. Collectively these results establish the two isoforms of GSK-3 as essential integrators of multiple developmental signals that act to maintain normal mammary gland function and suppress tumorigenesis.

scholarly journals Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion

2019 ◽  
Author(s):  
Parisa Rabieifar ◽  
Ting Zhuang ◽  
Tânia D. F. Costa ◽  
Miao Zhao ◽  
Staffan Strömblad
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Mammary Epithelium ◽  
Small Gtpases ◽  
Normal Mammary Gland ◽  
Knock Out ◽  
Adult Mice ◽  
Gland Development

Abstractp21-activated protein kinases (PAKs) are serine/threonine kinases functioning as downstream effectors of the small GTPases Rac1 and Cdc42. Members of the PAK family are overexpressed in human breast cancer, but their role in mammary gland development is not fully explored. Here we examined the functional role of PAK4 in mammary gland development by creating a mouse model of MMTV-Cre driven conditional PAK4 gene depletion in the mammary gland. The PAK4 conditional knock-out mice were born healthy with no observed developmental deficits. Mammary gland whole-mounts revealed no defects in ductal formation or elongation of the mammary tree through the fat pad. PAK4 gene depletion also did not alter proliferation and invasion of the mammary epithelium in young virgin mice. Moreover, adult mice gave birth to healthy pups with normal body weight upon weaning. This implies that MMTV-Cre induced gene depletion of PAK4 in mice does not impair normal mammary gland development and thereby provides an in vivo model for examination of the potential function of PAK4 in breast cancer.

scholarly journals Bovine mammary gland development: new insights into the epithelial hierarchy

2018 ◽  
Author(s):  
Laurence Finot ◽  
Eric Chanat ◽  
Frederic Dessauge
Keyword(s):  
Stem Cell ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Mammary Epithelium ◽  
Prolactin Receptors ◽  
Bovine Mammary Gland ◽  
Mammary Stem ◽  
Gland Development ◽  
Developmental Hierarchy

AbstractMilk production is highly dependent on the extensive development of the mammary epithelium, which occurs during puberty. It is therefore essential to distinguish the epithelial cells committed to development during this key stage from the related epithelial hierarchy. Using cell phenotyping and sorting, we highlighted three sub-populations that we assume to be progenitors. The CD49fhighCD24neg cells expressing KRT14, vimentin and PROCR corresponded to basal progenitors whereas the CD49flowCD24neg cells expressing luminal KRT, progesterone and prolactin receptors, were of luminal lineage. The CD49flowCD24pos cells had features of a dual lineage, with luminal and basal characteristics (CD10, ALDH1 and KRT7 expression) and were considered to be early common (bipotent) progenitors. The mammary stem cell (MaSC) fraction was recovered in a fourth sub-population of CD49fhighCD24pos cells that expressed CD10/KRT14 and KRT7. The differential ALDH1 activities observed within the MaSC fraction allowed to discriminate between two states: quiescent MaSCs and lineage-restricted “activated” MaSCs. The in-depth characterization of these epithelial sub-populations provides new insights into the epithelial cell hierarchy in the bovine mammary gland and suggests a common developmental hierarchy in mammals.

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