scholarly journals The Type 7 Serotonin Receptor, 5-HT7, Is Essential in the Mammary Gland for Regulation of Mammary Epithelial Structure and Function

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Vaibhav P. Pai ◽  
Laura L. Hernandez ◽  
Malinda A. Stull ◽  
Nelson D. Horseman
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Serotonin Receptor ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelium ◽  
Mammary Epithelial ◽  
Lactation Performance ◽  
Epithelial Structure ◽  
And Function ◽  
First Time

Autocrine-paracrine activity of serotonin (5-hydroxytryptamine, 5-HT) is a crucial homeostatic parameter in mammary gland development during lactation and involution. Published studies suggested that the 5-HT7receptor type was important for mediating several effects of 5-HT in the mammary epithelium. Here, using 5-HT7receptor-null (HT7KO) mice we attempt to understand the role of this receptor in mediating 5-HT actions within the mammary gland. We demonstrate for the first time that HT7KO dams are inefficient at sustaining their pups. Histologically, the HT7KO mammary epithelium shows a significant deviation from the normal secretory epithelium in morphological architecture, reduced secretory vesicles, and numerous multinucleated epithelial cells with atypically displaced nuclei, during lactation. Mammary epithelial cells in HT7KO dams also display an inability to transition from lactation to involution as normally seen by transition from a columnar to a squamous cell configuration, along with alveolar cell apoptosis and cell shedding. Our results show that 5-HT7is required for multiple actions of 5-HT in the mammary glands including core functions that contribute to changes in cell shape and cell turnover, as well as specialized secretory functions. Understanding these actions may provide new interventions to improve lactation performance and treat diseases such as mastitis and breast cancer.

scholarly journals Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47876 ◽  
Author(s):  
Sonia M. Rosenfield ◽  
Emma T. Bowden ◽  
Shani Cohen-Missner ◽  
Krissa A. Gibby ◽  
Virginie Ory ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
And Function

Developmental role of the SNF1-related kinase Hunk in pregnancy-induced changes in the mammary gland

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4493-4509
Author(s):  
H.P. Gardner ◽  
G.K. Belka ◽  
G.B. Wertheim ◽  
J.L. Hartman ◽  
S.I. Ha ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelium ◽  
Ovarian Hormones ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Serine Threonine Kinase ◽  
Proliferation And Differentiation ◽  
Induced Changes

The steroid hormones 17 beta-estradiol and progesterone play a central role in the pathogenesis of breast cancer and regulate key phases of mammary gland development. This suggests that developmental regulatory molecules whose activity is influenced by ovarian hormones may also contribute to mammary carcinogenesis. In a screen designed to identify protein kinases expressed in the mammary gland, we previously identified a novel SNF1-related serine/threonine kinase, Hunk (hormonally upregulated Neu-associated kinase). During postnatal mammary development, Hunk mRNA expression is restricted to a subset of mammary epithelial cells and is temporally regulated with highest levels of expression occurring during early pregnancy. In addition, treatment of mice with 17 beta-estradiol and progesterone results in the rapid and synergistic upregulation of Hunk expression in a subset of mammary epithelial cells, suggesting that the expression of this kinase may be regulated by ovarian hormones. Consistent with the tightly regulated pattern of Hunk expression during pregnancy, mammary glands from transgenic mice engineered to misexpress Hunk in the mammary epithelium manifest temporally distinct defects in epithelial proliferation and differentiation during pregnancy, and fail to undergo normal lobuloalveolar development. Together, these observations suggest that Hunk may contribute to changes in the mammary gland that occur during pregnancy in response to ovarian hormones.

scholarly journals Targeted Expression of GLI1 in the Mammary Gland Disrupts Pregnancy-induced Maturation and Causes Lactation Failure

2007 ◽  
Vol 282 (49) ◽  
pp. 36090-36101 ◽  
Author(s):  
Marie Fiaschi ◽  
Björn Rozell ◽  
Åsa Bergström ◽  
Rune Toftgård ◽  
Marika I. Kleman
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Hedgehog Signaling Pathway ◽  
Milk Protein Gene ◽  
Milk Protein Gene Expression ◽  
And Function

The Hedgehog signaling pathway regulates the development and function of numerous tissues and when mis-regulated causes tumorigenesis. To assess the role of a deregulated Hedgehog signaling pathway in the mammary gland we targeted the expression of the Hedgehog effector protein, GLI1, to mammary epithelial cells using a bigenic inducible system. A constitutively active Hedgehog signaling pathway resulted with 100% penetrance in an undifferentiated mammary lobuloalveolar network during pregnancy. GLI1-expressing transgenic females were unable to lactate and milk protein gene expression was essentially absent. The inability to lactate was permanent and independent of continued GLI1 transgene expression. An increased expression of the GLI1 response gene Snail coupled to reduced expression of E-cadherin and STAT5 in the transgenic mammary gland provides a likely molecular explanation, underlying the observed phenotypic changes. In addition, remodeling of the mammary gland after parturition was impaired and expression of GLI1 was associated with accumulation of cellular debris in the mammary ducts during involution, indicating a defect in the clearance of dead cells. Areas with highly proliferative epithelial cells were observed in mammary glands with induced expression of GLI1. Within such areas an increased frequency of cells expressing nuclear Cyclin D1 was observed. Taken together the data support the notion that correct regulation of Hedgehog signaling within the epithelial cell compartment is critical for pregnancy-induced mammary gland development and remodeling.

scholarly journals Correction: Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
Author(s):  
Sonia M. Rosenfield ◽  
Emma T. Bowden ◽  
Shani Cohen-Missner ◽  
Krissa A. Gibby ◽  
Virginie Ory ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
And Function

scholarly journals Mammary mechanobiology: mechanically-activated ion channels in lactation and involution

2019 ◽  
Author(s):  
Teneale A. Stewart ◽  
Katherine Hughes ◽  
Alexander J. Stevenson ◽  
Natascia Marino ◽  
Adler L. Ju ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Food Source ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Mechanical Forces ◽  
Offspring Survival ◽  
Evolutionary Advantage ◽  
And Function ◽  
Mechanical Sensing

AbstractA mother’s ability to produce a nutritionally-complete neonatal food source has provided a powerful evolutionary advantage to mammals. Milk production by secretory mammary epithelial cells is adaptive, its release is exquisitely timed and its own glandular stagnation with the permanent cessation of suckling triggers the programmed cell death and tissue remodeling that enables female mammals to nurse successive progeny. Both chemical and mechanical signals control epithelial expansion, function and remodeling. Despite this duality of input, however, the nature and function of mechanical forces in the mammary gland remain unknown. Here, we characterize the mammary force landscape and the capacity of luminal and basal epithelial cells to experience and exert force. We explore the molecular instruments for force-sensing in the mammary gland and the physiological requirement for PIEZO1 in lactation and involution. Our study supports the existence of a multifaceted system of chemical and mechanical sensing in the mammary gland, and a protective redundancy that ensures continued lactational competence and offspring survival.

scholarly journals Effects of Selenomethionine on Cell Viability, Selenoprotein Expression and Antioxidant Function in Porcine Mammary Epithelial Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Jun Chen ◽  
Yinzhi Zhang ◽  
Yantao Lv ◽  
Min Tian ◽  
Jinming You ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Glutathione Peroxidase ◽  
Cell Viability ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Antioxidant Enzyme Activities ◽  
Lactation Performance ◽  
Antioxidant Function

This study investigated the effects of selenomethionine (Se-Met) on the cell viability, selenoprotein expression, and antioxidant function of porcine mammary epithelial cells (pMECs) to reveal the underlying molecular mechanism of Se-Met on the lactation performance and antioxidant capacity of sows in vitro. The pMECs were used as an in vitro model and were treated with various concentrations of Se-Met (0, 0.5, 1, 2, and 4 μM). Cells were analyzed for cell viability, selenoprotein transcriptome, selenoprotein expression, and antioxidant enzyme activities. The results showed that, with increasing Se-Met concentrations, cell viability first increased and then decreased at 24, 48, or 72 h posttreatment with maximum values at 0.5-μM Se-Met. As the Se-Met concentrations increased, the mRNA expression of 17 selenoproteins first upregulated and then downregulated, with maximum values at 0.5-μM Se-Met. The 17 selenoproteins included SEPHS2, SELENOP, GPX1, GPX2, GPX3, GPX6, TXNRD1, SELENOK, SELENOW, DIO1, DIO2, DIO3, SELENOF, SELENOS, SELENOH, SELENOI, and SELENOT. Additionally, the protein expression levels of SEPHS2, SELENOP, GPX1, and TXNRD1 and the activities of glutathione peroxidase and thioredoxin were highest at 0.5-μM Se-Met. In conclusion, 0.5-μM Se-Met promotes cell viability partially by improving selenoprotein expression and antioxidant function in pMECs, which provides evidence for the potential ability of Se-Met to improve mammary gland health in sows.

scholarly journals Transduction of the Mammary Epithelium with Adenovirus Vectors In Vivo

2003 ◽  
Vol 77 (10) ◽  
pp. 5801-5809 ◽  
Author(s):  
Tanya D. Russell ◽  
Andreas Fischer ◽  
Neal E. Beeman ◽  
Emily F. Freed ◽  
Margaret C. Neville ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Fluorescent Protein ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelium ◽  
Normal Function ◽  
Mammary Epithelial ◽  
Intraductal Injection ◽  
Adenovirus Vectors

ABSTRACT Because the mammary parenchyma is accessible from the exterior of an animal through the mammary duct, adenovirus transduction holds promise for the short-term delivery of genes to the mammary epithelium for both research and therapeutic purposes. To optimize the procedure and evaluate its efficacy, an adenovirus vector (human adenovirus type 5) encoding a green fluorescent protein (GFP) reporter and deleted of E1 and E3 was injected intraductally into the mouse mammary gland. We evaluated induction of inflammation (by intraductal injection of [14C]sucrose and histological examination), efficiency of transduction, and maintenance of normal function in transduced cells. We found that transduction of the total epithelium in the proximal portion of the third mammary gland varied from 7% to 25% at a dose of 2 × 106 PFU of adenovirus injected into day 17 pregnant mice. Transduction was maintained for at least 7 days with minimal inflammatory response; however, significant mastitis was observed 12 days after transduction. Adenovirus transduction could also be used in the virgin animal with little mastitis 3 days after transduction. Transduced mammary epithelial cells maintained normal morphology and function. Our results demonstrate that intraductal injection of adenovirus vectors provides a versatile and noninvasive method of investigating genes of interest in mouse mammary epithelial cells.

scholarly journals Laminin alpha 5 is Necessary for Mammary Epithelial Growth and Function by Maintaining Luminal Epithelial Cell Identity

2019 ◽  
Author(s):  
Johanna I Englund ◽  
Hanne Cojoc ◽  
Leander Blaas ◽  
Alexandra Ritchie ◽  
Nalle Pentinmikko ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Normal Mammary Gland ◽  
Hormone Receptor Positive ◽  
And Function ◽  
Gland Development ◽  
Luminal Epithelial Cells ◽  
Basal Epithelial Cells

ABSTRACTEpithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet the exact roles of specific BM components remain unclear. Here, we demonstrate that expression of distinct laminin α-isoforms by luminal and basal mammary epithelial cells enforces lineage identity that is necessary for normal mammary gland growth and function. Laminin α5 (LMα5) is mainly expressed by the luminal epithelial cells, and it is necessary for pubertal mammary gland growth, pregnancy induced gland remodeling, and for alveolar function. Adhesion to LMα5 containing laminin promotes luminal traits in both luminal and basal epithelial cells, and reduces progenitor activity of basal epithelial cells. Mechanistically, we show that Lama5 loss interferes with differentiation of hormone receptor positive luminal cells, which results in reduced Wnt4 expression and defective crosstalk between luminal and basal epithelial cells during gland remodeling. Our results reveal a novel BM-mediated mechanism, which regulates mammary gland remodeling and function via specification of luminal epithelial cells.

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.

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