scholarly journals Transcriptional Response of the Murine Mammary Gland to Acute Progesterone Exposure

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6236-6250 ◽  
Author(s):  
Rodrigo Fernandez-Valdivia ◽  
Atish Mukherjee ◽  
Chad J. Creighton ◽  
Adam C. Buser ◽  
Francesco J. DeMayo ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Chromatin Immunoprecipitation ◽  
Transcriptional Response ◽  
Transcriptional Regulators ◽  
Mammary Epithelial ◽  
Epithelial Proliferation ◽  
Chromatin Immunoprecipitation Assay ◽  
Mammary Morphogenesis ◽  
Effector Pathways ◽  
Informational Resource

Our mechanistic understanding of progesterone’s involvement in murine mammary morphogenesis and tumorigenesis is dependent on defining effector pathways responsible for transducing the progesterone signal into a morphogenetic response. Toward this goal, microarray methods were applied to the murine mammary gland to identify novel downstream gene targets of progesterone. Consistent with a tissue undergoing epithelial expansion, mining of the progesterone-responsive transcriptome revealed the up-regulation of functional gene classes involved in epithelial proliferation and survival. Reassuringly, signaling pathways previously reported to be responsive to progesterone were also identified. Mining this informational resource for rapidly induced genes, we identified “inhibitor of differentiation 4” (Id4) as a new molecular target acutely induced by progesterone exposure. Mammary Id4 is transiently induced during early pregnancy and colocalizes with progesterone receptor (PR) expression, suggesting that Id4 mediates the early events of PR-dependent mammary morphogenesis. Chromatin immunoprecipitation assay detecting direct recruitment of ligand occupied PR to the Id4 promoter supports this proposal. Given that Id4 is a member of the Id family of transcriptional regulators that have been linked to the maintenance of proliferative status and tumorigenesis, the establishment of a mechanistic link between PR signaling and Id4 promises to furnish a wider conceptual framework with which to advance our understanding of normal and abnormal mammary epithelial responses to progestins. In sum, the progesterone-responsive transcriptome described herein not only reinforces the importance of progesterone in mammary epithelial expansion but also represents an invaluable information resource with which to identify novel signaling paradigms for mammary PR action.

scholarly journals Oct-1 Counteracts Autoinhibition of Runx2 DNA Binding To Form a Novel Runx2/Oct-1 Complex on the Promoter of the Mammary Gland-Specific Gene β-casein

2005 ◽  
Vol 25 (8) ◽  
pp. 3182-3193 ◽  
Author(s):  
Claire K. Inman ◽  
Na Li ◽  
Paul Shore
Keyword(s):  
Transcription Factor ◽  
Mammary Gland ◽  
Dna Binding ◽  
Chromatin Immunoprecipitation ◽  
Mammary Epithelial Cells ◽  
Bone Development ◽  
Mammary Epithelial ◽  
Specific Gene ◽  
Novel Complex ◽  
Complex Forms

ABSTRACT The transcription factor Runx2 is essential for the expression of a number of bone-specific genes and is primarily considered a master regulator of bone development. Runx2 is also expressed in mammary epithelial cells, but its role in the mammary gland has not been established. Here we show that Runx2 forms a novel complex with the ubiquitous transcription factor Oct-1 to regulate the expression of the mammary gland-specific gene β-casein. The Runx2/Oct-1 complex forms on a Runx/octamer element which is highly conserved in casein promoters. Chromatin immunoprecipitation, RNA interference, promoter mutagenesis, and transient expression analyses were used to demonstrate that the Runx2/Oct-1 complex contributes to the transcriptional regulation of the β-casein gene. Analysis of the complex revealed autoinhibitory domains for DNA binding in both the N-terminal and the C-terminal regions of Runx2. Oct-1 stimulates the recruitment of Runx2 to the β-casein promoter by interacting with the C-terminal region of Runx2, suggesting that Oct-1 stimulates Runx2 recruitment by relieving the autoinhibition of Runx2 DNA binding. These findings demonstrate that Runx2 collaborates with Oct-1 and contributes to the expression of a mammary gland-specific gene.

scholarly journals Effects of serum on mammary epithelial proliferation in vitro during mammary gland development.

1975 ◽  
Vol 66 (2) ◽  
pp. 243-250 ◽  
Author(s):  
H W Hsueh ◽  
F E Stockdale
Keyword(s):  
Mammary Gland ◽  
Proliferative Response ◽  
Mammary Epithelial ◽  
Serum Factor ◽  
Epithelial Proliferation ◽  
Hypophysectomized Rats ◽  
Gland Development ◽  
Proliferation In Vitro

The proliferative response of mammary gland epithelium from nonpregnant, pregnant, and lactating mice to mammary serum factor and insulin was studied in vitro. Mammary gland epiithelium from nonpregnant and lactating animals has a delayed proliferative response to mammary serum factor and insulin when compared to the response of epithelium from pregnant animals. The results show that as the animals go through pregnancy into lactation the mammary gland epithelium becomes less responsive to mammary serum factor while it retains its responsiveness to insulin. The concentration of mammary serum factor in sera from animals at various physiological stages is constant. Sera from hypophysectomized rats, on the other hand, show a 50% drop in mammary serum factor activity. This loss of activity cannot be reversed by injecting prolactin, 17-beta-estradiol, or growth hormone into the hypophysectomized animals. A hypothesis that the mammary gland is composed of two proliferative epithelial populations is developed, and the possible role of prolactin in stimulating DNA synthesis is discussed.

Respiration of epithelial component of mammary gland slices

1960 ◽  
Vol 199 (6) ◽  
pp. 1067-1069 ◽  
Author(s):  
E. Douglas Rees
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Mammary Tissue ◽  
Biological Parameters ◽  
Hydroxyproline Content ◽  
Epithelial Proliferation ◽  
Cell Component ◽  
Rat Mammary Gland

The respiration of slices from rat mammary gland was accounted for by the independent contributions of each of the three major components of mammary tissue: adipose, epithelial and connective. The contribution of each component was the amount of the component times its characteristic qo2. In the virgin mammary gland the adipose and connective tissue components accounted for the bulk of the observed respiration; but the qo2 increased directly and linearly with epithelial proliferation induced by various means—pregnancy, lactation, or administration of progesterone or estradiol-17ß. An equation containing only biological parameters and relating qo2 to hydroxyproline content of mammary gland was derived. A qo2 value of 14.2 ± 1.8 for the mammary epithelial cell component was obtained.

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.

Ultrastructural Changes in the Mammary Epithelial Cell Population During Neoplastic Development Induced by A Chemical Carcinogen.

1976 ◽  
Vol 34 ◽  
pp. 250-251 ◽  
Author(s):  
J. Russo ◽  
W. Isenberg ◽  
M. Ireland ◽  
I.H. Russo
Keyword(s):  
Mammary Gland ◽  
Cell Population ◽  
Virgin Female ◽  
Histological Change ◽  
Mammary Epithelial ◽  
Female Rats ◽  
Ultrastructural Changes ◽  
Post Inoculation ◽  
Chemical Carcinogen ◽  
Sprague Dawley

The induction of rat mammary carcinoma by the chemical carcinogen DMBA is used as a model for the study of the human disease (1). We previously described the histochemical changes that occur in the mammary gland of DMBA treated animals before the earliest manifested histological change, the intraductal proliferation (IDP), was observed (2). In the present work, we demonstrate that a change in the stable cell population found in the resting mammary gland occurs after carcinogen administration.Fifty-five day old Sprague-Dawley virgin female rats were inoculated intragastrically with 20mg of 7,12-dimethylbenz(a)anthracene (DMBA) in 1ml sesame oil. Non-inoculated, age-matched females were used as controls. Mammary glands from control and inoculated rats were removed weekly from the time of inoculation until 60 days post-inoculation. For electron microscopy, the glands were immersed in Karnovsky's fixative, post-fixed in 1% OsO4, dehydrated, and embedded in an Epon-Araldite mixture. Thick (lμ) sections were stained with 1% toluidine blue and were used for selecting areas for ultrastructural study.

scholarly journals Evidence of Rab3A Expression, Regulation of Vesicle Trafficking, and Cellular Secretion in Response to Heregulin in Mammary Epithelial Cells

2000 ◽  
Vol 20 (23) ◽  
pp. 9092-9101 ◽  
Author(s):  
Ratna K. Vadlamudi ◽  
Rui-An Wang ◽  
Amjad H. Talukder ◽  
Liana Adam ◽  
Randy Johnson ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Vesicle Trafficking ◽  
Mammary Epithelial ◽  
Coated Vesicle ◽  
Human Breast ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Stimulation Of

ABSTRACT Heregulin β1 (HRG), a combinatorial ligand for human growth factor receptors 3 and 4, is a regulatory polypeptide that promotes the differentiation of mammary epithelial cells into secretory lobuloalveoli. Emerging evidence suggests that the processes of secretory pathways, such as biogenesis and trafficking of vesicles in neurons and adipose cells, are regulated by the Rab family of low-molecular-weight GTPases. In this study, we identified Rab3A as a gene product induced by HRG. Full-length Rab3A was cloned from a mammary gland cDNA library. We demonstrated that HRG stimulation of human breast cancer cells and normal breast epithelial cells induces the expression of Rab3A protein and mRNA in a cycloheximide-independent manner. HRG-mediated induction of Rab3A expression was blocked by an inhibitor of phosphatidylinositol 3-kinase but not by inhibitors of mitogen-activated protein kinases p38MAPK and p42/44MAPK. Human breast epithelial cells also express other components of regulated vesicular traffic, such as rabphilin 3A, Doc2, and syntaxin. Rab3A was predominantly localized in the cytosol, and HRG stimulation of the epithelial cells also raised the level of membrane-bound Rab3A. HRG treatment induced a profound alteration in the cell morphology in which cells displayed neuron-like membrane extensions that contained Rab3A-coated, vesicle-like structures. In addition, HRG also promoted the secretion of cellular proteins from the mammary epithelial cells. The ability of HRG to modify exocytosis was verified by using a growth hormone transient-transfection system. Analysis of mouse mammary gland development revealed the expression of Rab3A in mammary epithelial cells. Furthermore, expression of the HRG transgene in Harderian tumors in mice also enhanced the expression of Rab3A. These observations provide new evidence of the existence of a Rab3A pathway in mammary epithelial cells and suggest that it may play a role in vesicle trafficking and secretion of proteins from epithelial cells in response to stimulation by the HRG expressed within the mammary mesenchyma.

MicroRNA-432 inhibits milk fat synthesis by targeting SCD and LPL in ovine mammary epithelial cells

2021 ◽  
Author(s):  
Zhiyun Hao ◽  
Yuzhu Luo ◽  
Jiqing Wang ◽  
Jon Hickford ◽  
Huitong Zhou ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Milk Production ◽  
Milk Fat ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Fat Synthesis ◽  
Milk Fat Synthesis

In our previous studies, microRNA-432 (miR-432) was found to be one of differentially expressed miRNAs in ovine mammary gland between the two breeds of lactating sheep with different milk production...

Bovine mammary epithelial cells, initiators of innate immune responses to mastitis

2005 ◽  
Vol 45 (8) ◽  
pp. 757 ◽  
Author(s):  
C. Gray ◽  
Y. Strandberg ◽  
L. Donaldson ◽  
R. L. Tellam
Keyword(s):  
Immune Response ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Vital Role ◽  
Mammary Epithelial ◽  
Innate Immune ◽  
Mammary Tissue ◽  
Effector Cells ◽  
Bovine Mammary Epithelial Cells

Innate immunity plays a vital role in the protection of the bovine mammary gland against mastitis. Until recently, the migration of effector cells such as neutrophils and monocytes into the mammary gland was thought to provide the only defence against invading pathogens. However, mammary epithelial cells may also play an important role in the immune response, contributing to the innate defence of the mammary tissue through secretion of antimicrobial peptides and attraction of circulating immune effector cells. This paper reviews the innate immune pathways in mammary epithelial cells and examines their role in the initiation of an innate immune response to Gram-positive and Gram-negative bacteria.

Sign in / Sign up

Export Citation Format

Share Document