Epithelial p53 Status Modifies Stromal-Epithelial Interactions During Basal-Like Breast Carcinogenesis
AbstractBasal-like breast cancers (BBC) exhibit subtype-specific phenotypic and transcriptional responses to stroma, but little research has addressed how stromal-epithelial interactions evolve during early BBC carcinogenesis. It is also unclear how common genetic defects, such as p53 mutations, modify these stromal-epithelial interactions. To address these knowledge gaps, we leveraged the MCF10 progression series of breast cell lines (MCF10A, MCF10AT1, and MCF10DCIS) to develop a longitudinal, tissue-contextualized model of p53-deficient, pre-malignant breast. Acinus asphericity, a morphogenetic correlate of cell invasive...
Source: Journal of Mammary Gland Biology and Neoplasia - January 13, 2021 Category: Cancer & Oncology Source Type: research

Cancer-Associated Fibroblasts in the Breast Tumor Microenvironment
AbstractYears of investigation have shed light on a theory in which breast tumor epithelial cells are under the effect of the stromal microenvironment. This review aims to discuss recent findings concerning the phenotypic and functional characteristics of cancer associated fibroblasts (CAFs) and their involvement in tumor evolution, as well as their potential implications for anti-cancer therapy. In this manuscript, we reviewed that CAFs play a fundamental role in initiation, growth, invasion, and metastasis of breast cancer, and also serve as biomarkers in the clinical diagnosis, therapy, and prognosis of this disease. (S...
Source: Journal of Mammary Gland Biology and Neoplasia - January 4, 2021 Category: Cancer & Oncology Source Type: research

Morphological Analysis of Human Milk Membrane Enclosed Structures Reveals Diverse Cells and Cell-like Milk Fat Globules
AbstractOver the past decade, the cellular content of human milk has been a focus in lactation research due to the benefit a potential non-invasive stem cell compartment could provide either to the infant or for therapeutic applications. Despite an increase in the number of studies in this field, fundamental knowledge in regard to milk cell identification and characterisation is still lacking. In this project, we investigated the nature, morphology and content of membrane enclosed structures (MESs) and explored different methods to enrich human milk cells (HMCs) whilst reducing milk fat globule (MFG) content. Using both fl...
Source: Journal of Mammary Gland Biology and Neoplasia - January 4, 2021 Category: Cancer & Oncology Source Type: research

Recent Advances in Experimental Models of Breast Cancer Exosome Secretion, Characterization and Function
AbstractBreast cancer (BC) is responsible for 15% of all the cancer deaths among women in the USA. The tumor microenvironment (TME) has the potential to act as a driver of breast cancer progression and metastasis. The TME is composed of stromal cells within an extracellular matrix and soluble cytokines, chemokines and extracellular vesicles and nanoparticles that actively influence cell behavior. Extracellular vesicles include exosomes, microvesicles and large oncosomes that orchestrate fundamental processes during tumor progression through direct interaction with target cells. Long before tumor cell spread to future metas...
Source: Journal of Mammary Gland Biology and Neoplasia - December 22, 2020 Category: Cancer & Oncology Source Type: research

Methodological Advancements for Investigating Intra-tumoral Heterogeneity in Breast Cancer at the Bench and Bedside
AbstractThere is a major need to overcome therapeutic resistance and metastasis that eventually arises in many breast cancer patients. Therapy resistant and metastatic tumors are increasingly recognized to possess intra-tumoral heterogeneity (ITH), a diversity of cells within an individual tumor. First hypothesized in the 1970s, the possibility that this complex ITH may endow tumors with adaptability and evolvability to metastasize and evade therapies is now supported by multiple lines of evidence. Our understanding of ITH has been driven by recent methodological advances including next-generation sequencing, computational...
Source: Journal of Mammary Gland Biology and Neoplasia - December 9, 2020 Category: Cancer & Oncology Source Type: research

Development and Pathology of the Equine Mammary Gland
AbstractAn understanding of the anatomy, histology, and development of the equine mammary gland underpins study of the pathology of diseases including galactorrhoea, agalactia, mastitis, and mammary tumour development. This review examines the prenatal development of the equine mammary gland and the striking degree to which the tissue undergoes postnatal development associated with the reproductive cycle. The gland is characterised by epithelial structures arranged in terminal duct lobular units, similar to those of the human breast, supported by distinct zones of intra- and interlobular collagenous stroma. Mastitis and ma...
Source: Journal of Mammary Gland Biology and Neoplasia - December 5, 2020 Category: Cancer & Oncology Source Type: research

Single Cell RNA Sequencing of Human Milk-Derived Cells Reveals Sub-Populations of Mammary Epithelial Cells with Molecular Signatures of Progenitor and Mature States: a Novel, Non-invasive Framework for Investigating Human Lactation Physiology
AbstractCells in human milk are an untapped source, as potential “liquid breast biopsies”, of material for investigating lactation physiology in a non-invasive manner. We used single cell RNA sequencing (scRNA-seq) to identify milk-derived mammary epithelial cells (MECs) and their transcriptional signatures in women with diet-controlled gestational diabetes ( GDM) with normal lactation. Methodology is described for coordinating milk collections with single cell capture and library preparation via cryopreservation, in addition to scRNA-seq data processing and analyses of MEC transcriptional signatures. We compre...
Source: Journal of Mammary Gland Biology and Neoplasia - November 20, 2020 Category: Cancer & Oncology Source Type: research

Got Milk? Identifying and Characterizing Lactation Defects in Genetically-Engineered Mouse Models
AbstractThe ability to produce and expel milk is important for the health and survival of all mammals. Nevertheless, our understanding of the molecular events underlying the execution of this process remains incomplete. Whilst impaired mammary gland development and lactational competence remains the subject of focused investigations, defects in these events may also be an unintended consequence of genetic manipulation in rodent models. In this technical report, we outline established and emerging methods to characterize lactation phenotypes in genetically-engineered mouse models. We discuss important considerations of comm...
Source: Journal of Mammary Gland Biology and Neoplasia - November 19, 2020 Category: Cancer & Oncology Source Type: research

Mammary Organoids and 3D Cell Cultures: Old Dogs with New Tricks
Abstract3D cell culture methods have been an integral part of and an essential tool for mammary gland and breast cancer research for half a century. In fact, mammary gland researchers, who discovered and deciphered the instructive role of extracellular matrix (ECM) in mammary epithelial cell functional differentiation and morphogenesis, were the pioneers of the 3D cell culture techniques, including organoid cultures. The last decade has brought a tremendous increase in the 3D cell culture techniques, including modifications and innovations of the existing techniques, novel biomaterials and matrices, new technological appro...
Source: Journal of Mammary Gland Biology and Neoplasia - November 18, 2020 Category: Cancer & Oncology Source Type: research

Intraductal Injection of Lentivirus Vectors for Stably Introducing Genes into Rat Mammary Epithelial Cells in Vivo
AbstractVarious retroviral and lentiviral vectors have been used for up-the-teat intraductal injection to deliver markers, oncogenes, and other genes into mammary epithelial cells in mice. These methods along with the large number of genetically engineered mouse lines have greatly helped us learn normal breast development and tumorigenesis. Rats are also valuable models for studying human breast development and cancer. However, genetically engineered rats are still uncommon, and previous reports of intraductal injection of retroviral vectors into rats appear to be inefficient in generating mammary tumors. Here, we report, ...
Source: Journal of Mammary Gland Biology and Neoplasia - November 9, 2020 Category: Cancer & Oncology Source Type: research

Preclinical Models to Study Obesity and Breast Cancer in Females: Considerations, Caveats, and Tools
We describe relevant mouse and rat paradigms, specifically highlighting differences in breast tumor subtypes, estrogen production, and strategies to manipulate hormone levels. We also outline options for diet composition and housing environments to promote obesity in female rodents. While we have applied our experience to understanding obesity-associated breast cancer, the experimental variables we incorporate have relevance to multiple fields that investigate women ’s health. (Source: Journal of Mammary Gland Biology and Neoplasia)
Source: Journal of Mammary Gland Biology and Neoplasia - November 4, 2020 Category: Cancer & Oncology Source Type: research

Characterization of Organoid Cultures to Study the Effects of Pregnancy Hormones on the Epigenome and Transcriptional Output of Mammary Epithelial Cells
AbstractThe use of mouse derived mammary organoids can provide a unique strategy to study mammary gland development across a normal life cycle, as well as offering insights into how malignancies form and progress. Substantial cellular and epigenomic changes are triggered in response to pregnancy hormones, a reaction that engages molecular and cellular changes that transform the mammary epithelial cells into “milk producing machines”. Such epigenomic alterations remain stable in post-involution mammary epithelial cells and control the reactivation of gene transcription in response to re-exposure to pregnancy hor...
Source: Journal of Mammary Gland Biology and Neoplasia - November 1, 2020 Category: Cancer & Oncology Source Type: research

Optimal, Large-Scale Propagation of Mouse Mammary Tumor Organoids
AbstractTumor organoids mimic the architecture and heterogeneity of in vivo tumors and enable studies of collective interactions between tumor cells as well as with their surrounding microenvironment. Although tumor organoids hold significant promise as cancer models, they are also more costly and labor-intensive to cultivate than traditional 2D cell culture. We sought to identify critical factors regulating organoid growth ex vivo, and to use these observations to develop a more efficient organoid expansion method. Using time-lapse imaging of mouse mammary tumor organoids in 3D culture, we observed that outgrowth potentia...
Source: Journal of Mammary Gland Biology and Neoplasia - October 26, 2020 Category: Cancer & Oncology Source Type: research

May Their Lineages Live on – an Editorial Board Tribute to Zena Werb and Gil Smith
(Source: Journal of Mammary Gland Biology and Neoplasia)
Source: Journal of Mammary Gland Biology and Neoplasia - October 23, 2020 Category: Cancer & Oncology Source Type: research

Studying Lymphatic Metastasis in Breast Cancer: Current Models, Strategies, and Clinical Perspectives
AbstractBreast cancer is the most commonly diagnosed cancer in women and the second most common cause of cancer-related deaths in the United States. Although early detection has significantly decreased breast cancer mortality, patients diagnosed with distant metastasis still have a very poor prognosis. The most common site that breast cancer spreads to are local lymph nodes. Therefore, the presence of lymph node metastasis remains one of most important prognostic factors in breast cancer patients. Given its significant clinical implications, increased efforts have been dedicated to better understand the molecular mechanism...
Source: Journal of Mammary Gland Biology and Neoplasia - October 9, 2020 Category: Cancer & Oncology Source Type: research

In Memoriam - Gilbert Howlett Smith 1938-2020
(Source: Journal of Mammary Gland Biology and Neoplasia)
Source: Journal of Mammary Gland Biology and Neoplasia - October 5, 2020 Category: Cancer & Oncology Source Type: research

Protocol: Adeno-Associated Virus-Mediated Gene Transfer in Ex Vivo Cultured Embryonic Mammary Gland
AbstractBranching morphogenesis of the murine mammary gland starts during late embryogenesis. It is regulated by the signals emanating both from the epithelium and the mesenchyme, yet the molecular mechanisms regulating this process remain poorly understood. We have previously developed a unique whole organ culture technique for embryonic mammary glands, which provides a powerful tool to monitor and manipulate branching morphogenesis ex vivo. Nowadays, RNA sequencing and other transcriptional profiling techniques provide robust methods to identify components of gene regulatory networks driving branching morphogenesis. Howe...
Source: Journal of Mammary Gland Biology and Neoplasia - October 1, 2020 Category: Cancer & Oncology Source Type: research

In Memoriam - Zena Werb 1945 –2020
(Source: Journal of Mammary Gland Biology and Neoplasia)
Source: Journal of Mammary Gland Biology and Neoplasia - September 29, 2020 Category: Cancer & Oncology Source Type: research

Distinct Expression Patterns of Fibrillar Collagen Types I, III, and V in Association with Mammary Gland Remodeling during Pregnancy, Lactation and Weaning
In this study, we investigated their expression patterns during pregnancy, parturition, lactation and involution. Type I collagen showed a well-developed fibril structure during pregnancy, but the fibrillar structure of type I collagen then became sparse at parturition and during lactation, which was concurrent with the downregulation of its mRNA and protein levels. The well-developed fibrillar structure of type I collagen reappeared after weaning. On the other hand, type V collagen showed a well-developed fibrillar structure and upregulation in the lactation period but not in the periods of pregnancy and involution. Type ...
Source: Journal of Mammary Gland Biology and Neoplasia - September 10, 2020 Category: Cancer & Oncology Source Type: research

The Multi-Faced Role of PAPP-A in Post-Partum Breast Cancer: IGF-Signaling is Only the Beginning
AbstractInsulin-like growth factor (IGF) signaling and control of local bioavailability of free IGF by the IGF binding proteins (IGFBP) are important regulators of both mammary development and breast cancer. A recent genome-wide association study (GWAS) identified small nucleotide polymorphisms that reduce the expression of IGFBP-5 as a risk factor of developing breast cancer. This observation suggests that genetic alterations leading to a decreased level of IGFBP-5 may also contribute to breast cancer. In the current review, we focus onPregnancy-AssociatedPlasmaProteinA (PAPP-A), a protease involved in the degradation of ...
Source: Journal of Mammary Gland Biology and Neoplasia - September 7, 2020 Category: Cancer & Oncology Source Type: research

H2AX Promoter Demethylation at Specific Sites Plays a Role in STAT5-Induced Tumorigenesis
AbstractDeregulated STAT5 activity in the mammary gland of transgenic mice results in parity-dependent latent tumorigenesis. The trigger for cell transformation was previously associated with hyperactivation of the H2AX proximal promoter in a small basal cell population during pregnancy. The current study focuses on the latent activation of tumor development. H2AX was highly expressed in carcinoma and adenocarcinoma as compared to the multiparous mammary gland, whereas pSTAT5 expression decreased in a tumor type-dependent manner. In contrast to the pregnant gland, no positive correlation between H2AX and pSTAT5 expression ...
Source: Journal of Mammary Gland Biology and Neoplasia - August 2, 2020 Category: Cancer & Oncology Source Type: research

Hoxd10 Is Required Systemically for Secretory Activation in Lactation and Interacts Genetically with Hoxd9
AbstractTargeted disruption of the murineHoxd10 gene( ΔHoxd10) leads to a high frequency of localized (gland-to-gland or regionally within a gland) lactation impairment in homozygous mutant mice as a single gene mutation. The effect ofHoxd10 disruption was enhanced by simultaneous disruption ofHoxd9 ( ΔHoxd9/d10), a mutation shown previously to have no effect on mammary function as a single gene alteration. Mammary glands of homozygousΔHoxd10 andΔHoxd9/d10 females were indistinguishable from those of wild type littermate and age-matched control mice in late pregnancy. However, in lactation, 47% of h...
Source: Journal of Mammary Gland Biology and Neoplasia - July 22, 2020 Category: Cancer & Oncology Source Type: research

Intraductal Therapy in Breast Cancer: Current Status and Future Prospective
This article reviews the current status and future prospects of intraductal therapy in breast cancer, with emphasis on ductal carcinoma in situ. (Source: Journal of Mammary Gland Biology and Neoplasia)
Source: Journal of Mammary Gland Biology and Neoplasia - June 22, 2020 Category: Cancer & Oncology Source Type: research

Macphatics and PoEMs in Postpartum Mammary Development and Tumor Progression
In this report, we describe a subset of postpartum macrophages that express lymphatic proteins (PoEMs) and directly interact with lymphatic vessels to form chimeric vessels or “macphatics”. Additionally, th ese PoEMs are very similar to tumor-associated macrophages that also express lymphatic proteins and are present at the sites of lymphatic vessels where tumors escape the tissue and enter the lymphatic vasculature. Further characterizing these PoEMs may offer insight in preventing lymphatic metastasi s of breast cancer, as well as provide information for how developmental programming of lymphatic endothelial ...
Source: Journal of Mammary Gland Biology and Neoplasia - June 12, 2020 Category: Cancer & Oncology Source Type: research

Weighing the Risk: effects of Obesity on the Mammary Gland and Breast Cancer Risk
AbstractObesity is a preventable risk factor for breast cancer following menopause. Regardless of menopausal status, obese women who develop breast cancer have a worsened prognosis. Breast tissue is comprised of mammary epithelial cells organized into ducts and lobules and surrounded by adipose-rich connective tissue. Studies utilizing multiplein vivo models of obesity as well as human breast tissue have contributed to our understanding of how obesity alters mammary tissue. Localized changes in mammary epithelial cell populations, elevated secretion of adipokines and angiogenic mediators, inflammation within mammary adipos...
Source: Journal of Mammary Gland Biology and Neoplasia - June 8, 2020 Category: Cancer & Oncology Source Type: research

Breast Pathology That Contributes to Dysfunction of Human Lactation: a Spotlight on Nipple Blebs
AbstractNipple blebs are blister-like fibrinous lesions that form on the surface of the nipple during lactation, and can result in orifice obstruction and mastitis. They likely result from superficial extension of underlying ductal plugging, and can present concurrently with hyperlactation and mammary dysbiosis. Despite their prevalence, few formal reports on nipple blebs exist. In this perspective, we review the experience of a breastfeeding medicine practice that receives referrals for patients with nipple blebs, and provide preliminary insight into etiology, management, and outcomes of these lesions. (Source: Journal of...
Source: Journal of Mammary Gland Biology and Neoplasia - June 2, 2020 Category: Cancer & Oncology Source Type: research

Two Sides of the Same Coin: The Role of Developmental pathways and pluripotency factors in normal mammary stem cells and breast cancer metastasis
AbstractBreast cancer initiation and progression are often observed as the result of dysregulation of normal developmental processes and pathways. Studies focused on normal mammary stem/progenitor cell activity have led to an understanding of how breast cancer cells acquire stemness-associated properties including tumor initiation, survival and multi-lineage differentiation into heterogeneous tumors that become difficult to target therapeutically. Importantly, more recent investigations have provided valuable insight into how key developmental regulators can impact multiple phases of metastasis, where they are repurposed t...
Source: Journal of Mammary Gland Biology and Neoplasia - April 21, 2020 Category: Cancer & Oncology Source Type: research

Identification of an AP1-ZFP36 Regulatory Network Associated with Breast Cancer Prognosis
AbstractIt has been established that ZFP36 (also known as Tristetraprolin or TTP) promotes mRNA degradation of proteins involved in inflammation, proliferation and tumor invasiveness. In mammary epithelial cellsZFP36 expression is induced by STAT5 activation during lactogenesis, while in breast cancerZFP36 expression is associated with lower grade and better prognosis. Here, we show that the AP-1 transcription factor components, i.e.JUN, JUNB, FOS, FOSB, in addition toDUSP1, EGR1, NR4A1,IER2 andBTG2, behave as a conserved co-regulated group of genes whose expression is associated toZFP36 in cancer cells. In fact, a signifi...
Source: Journal of Mammary Gland Biology and Neoplasia - April 3, 2020 Category: Cancer & Oncology Source Type: research

Inter-Individual Variation in Response to Estrogen in Human Breast Explants
AbstractExposure to estrogen is strongly associated with increased breast cancer risk. While all women are exposed to estrogen, only 12% are expected to develop breast cancer during their lifetime. These women may be more sensitive to estrogen, as rodent models have demonstrated variability in estrogen sensitivity. Our objective was to determine individual variation in expression of estrogen receptor (ER) and estrogen-induced responses in the normal human breast. Human breast tissue from female donors undergoing reduction mammoplasty surgery were collected for microarray analysis of ER expression. To examine estrogen-induc...
Source: Journal of Mammary Gland Biology and Neoplasia - March 8, 2020 Category: Cancer & Oncology Source Type: research

Expression and Circulating Levels of Perlecan in Breast Cancer - Implications for Oestrogen Dependent Stromal Remodeling
This study shows that perlecan expression and degradation in breast cancer may be linked to the ER status of the tumour. (Source: Journal of Mammary Gland Biology and Neoplasia)
Source: Journal of Mammary Gland Biology and Neoplasia - March 1, 2020 Category: Cancer & Oncology Source Type: research

Orthotopic Implantation Achieves Better Engraftment and Faster Growth Than Subcutaneous Implantation in Breast Cancer Patient-Derived Xenografts
We present our OS implantation method in detail. The re-transplantation rate of TN tumors in each transplant site was significantly higher in OS when compared to SQ tumors (70.1% vs. 32.1%,p 
Source: Journal of Mammary Gland Biology and Neoplasia - February 26, 2020 Category: Cancer & Oncology Source Type: research

Ret Receptor Has Distinct Alterations and Functions in Breast Cancer
AbstractRet receptor tyrosine kinase is a proto-oncogene that participates in development of various cancers. Several independent studies have recently identified Ret as a key player in breast cancer. Although Ret overexpression and function have been under investigation, mainly in estrogen receptor positive breast cancer, a more comprehensive analysis of the impact of recurring Ret alterations in breast cancer is needed. This review consolidates the current knowledge of Ret alterations and their potential effects in breast cancer. We discuss and integrate data on Ret changes in different breast cancer subtypes and potenti...
Source: Journal of Mammary Gland Biology and Neoplasia - February 20, 2020 Category: Cancer & Oncology Source Type: research

C/EBP ß Isoform Specific Gene Regulation: It’s a Lot more Complicated than you Think!
AbstractIt has been almost 30  years since C/EBPß was discovered. Seminal studies have shown that C/EBPß is a master regulator of mammary gland development and has been shown to control and influence proliferation and differentiation through varying mechanisms. The single-exon C/EBPß mRNA yields at least three different prot ein isoforms which have diverse, specific, context-dependent, and often non-overlapping roles throughout development and breast cancer progression. These roles are dictated by a number of complex factors including: expression levels of other C/EBP family members and their stoichi...
Source: Journal of Mammary Gland Biology and Neoplasia - February 19, 2020 Category: Cancer & Oncology Source Type: research

The Novel Transcription Factor CREB3L4 Contributes to the Progression of Human Breast Carcinoma
AbstractBreast carcinoma(BC)is the most common cancer type among females globally. Understanding the molecular pathways that trigger the development of BC is crucial for both prevention and treatment. As such, the role of transcription factors (TFs) in the development of BC is a focal point in this field. CREB3s play a critical role in initiating the unfolded protein response (UPR); however, the role of CREB3 family members in breast cancer development remains largely unknown. Here, we mined the ONCOMINE database for the transcriptional data of CREB3s in patients with BC. Then, the regulatory functions of a novel TF, CREB3...
Source: Journal of Mammary Gland Biology and Neoplasia - February 5, 2020 Category: Cancer & Oncology Source Type: research

Calcification Microstructure Reflects Breast Tissue Microenvironment
This study explores the hypothesis that microenvironment features may become immortalised within calcification crystallite characteristics thus becoming indicators of tissue pathology. In total, 55 breast calcifications incorporating 3 tissue pathologies (benign – B2, ductal carcinoma in-situ - B5a and invasive malignancy - B5b) from archive formalin-fixed paraffin-embedded core needle breast biopsies were analysed using X-ray diffraction. Crystallite size and strain were determined from 548 diffractograms using Williamson-Hall analysis. There was an incr eased crystallinity of hydroxyapatite with tissue malignancy c...
Source: Journal of Mammary Gland Biology and Neoplasia - December 4, 2019 Category: Cancer & Oncology Source Type: research

Circ-TFCP2L1 Promotes the Proliferation and Migration of Triple Negative Breast Cancer through Sponging miR-7 by Inhibiting PAK1
In this study, we explored the circRNA expression profiles and possible modulation mechanism of circRNAs on triple negative breast cancer tumourigenesis. We used three pairs of triple negative breast cancer tissues and adjacent noncancerous tissues to perform a human circRNA microarray for screening of circRNA expression patterns in TNBC. The results showed that circ-TFCP2L1 was significantly up-regulated in TNBC tissues and cells, tending to have a shorter disease-free survival of TNBC patients. In vitro loss-of-function experiments showed that knockdown of circ-TFCP2L1 significantly suppressed the proliferation and migra...
Source: Journal of Mammary Gland Biology and Neoplasia - November 26, 2019 Category: Cancer & Oncology Source Type: research

Exogenous ER α Expression in the Mammary Epithelium Decreases Over Time and Does Not Contribute to p53-Deficient Mammary Tumor Formation in Mice
AbstractApproximately 75% of all breast cancers express the nuclear hormone receptor estrogen receptor α (ERα). However, the majority of mammary tumors from genetically engineered mouse models (GEMMs) are ERα-negative. To model ERα-positive breast cancer in mice, we exogenously introduced expression of mouse and human ERα in an existing GEMM of p53-deficient breast cancer. After initial ERα exp ression during mammary gland development, expression was reduced or lost in adult glands and p53-deficient mammary tumors. Chromatin immunoprecipitation (ChIP)-sequencing analysis of primary mouse...
Source: Journal of Mammary Gland Biology and Neoplasia - November 14, 2019 Category: Cancer & Oncology Source Type: research

Redirecting Normal and Cancer Stem Cells to a Mammary Epithelial Cell Fate
AbstractTissue microenvironments, also known as stem cell niches, influence not only resident cells but also cells in surrounding tissues. Physical and biochemical intercellular signals originating from resident stem cells or non-stem cells participate in the homeostasis of the tissue regulating cell proliferation, differentiation, wound healing, tissue remodeling, and tumorigenesis. In recent publications it has been demonstrated that the normal mouse mammary microenvironment can provide development and differentiation guidance to not only resident mammary cells but also cells of non-mammary origin including tumor-derived...
Source: Journal of Mammary Gland Biology and Neoplasia - November 14, 2019 Category: Cancer & Oncology Source Type: research

Electron Tomography Revels that Milk Lipids Originate from Endoplasmic Reticulum Domains with Novel Structural Features
AbstractLipid droplets (LD) are dynamically-regulated organelles that originate from the endoplasmic reticulum (ER), and function in the storage, trafficking and metabolism of neutral lipids. In mammary epithelial cells (MEC) of lactating animals, intact LD are secreted intact into milk to form milk lipids by a novel apocrine mechanism. The secretion of intact LD and the relatively large amounts of lipid secreted by lactating MEC increase demands on the cellular processes responsible for lipid synthesis and LD formation. As yet these processes are poorly defined due to limited understanding of LD-ER interactions. To overco...
Source: Journal of Mammary Gland Biology and Neoplasia - November 9, 2019 Category: Cancer & Oncology Source Type: research

The Milk Protein Alpha-Casein Suppresses Triple Negative Breast Cancer Stem Cell Activity Via STAT and HIF-1alpha Signalling Pathways in Breast Cancer Cells and Fibroblasts
We examined the effects of the milk protein alpha-casein over expression in the triple negative MDA-MB-231 breast cancer cell line. The effects of recombinant alpha-casein added exogenously to MDA-MB-231 breast cancer cells, and immortalised human fibroblasts were also investigated. We used transcriptional reporters to understand the signalling pathways downstream of alpha-casein in breast cancer cells and these fibroblasts that were activated by breast cancer cells. To extend our findings to the clinical setting, we analysed public gene expression datasets to further understand the relevance of these signalling pathways i...
Source: Journal of Mammary Gland Biology and Neoplasia - September 11, 2019 Category: Cancer & Oncology Source Type: research

Remodeling of Murine Mammary Adipose Tissue during Pregnancy, Lactation, and Involution
AbstractWhite adipocytes in the mammary gland stroma comprise the majority of the mammary gland mass. White adipocytes regulate numerous hormonal and metabolic processes and exhibit compositional and phenotypic plasticity. This plasticity is exemplified by the ability of mammary adipocytes to regress during lactation, when mammary epithelial cells expand to establish sufficient milk-producing alveoli. Upon weaning, the process reverses through mammary involution, during which adipocytes extensively regenerate, and alveolar epithelial cells disappear through cell death, returning the mammary gland to the non-lactating state...
Source: Journal of Mammary Gland Biology and Neoplasia - September 11, 2019 Category: Cancer & Oncology Source Type: research

The Eleventh ENBDC Workshop: Advances in Technology Help to Unveil Mechanisms of Mammary Gland Development and Cancerogenesis
AbstractThe eleventh annual workshop of the European Network for Breast Development and Cancer,Methods in mammary gland biology and breast cancer, took place on the 16th to 18th of May 2019 in Weggis, Switzerland. The main topics of the meeting were high resolution genomics and proteomics for the study of mammary gland development and cancer, breast cancer signaling, tumor microenvironment, preclinical models of breast cancer, and tissue morphogenesis. Exciting novel findings in, or highly relevant to, mammary gland biology and breast cancer field were presented, with insights into the methods used to obtain them. Among ot...
Source: Journal of Mammary Gland Biology and Neoplasia - September 6, 2019 Category: Cancer & Oncology Source Type: research

How to Choose a Mouse Model of Breast Cancer, a Genomic Perspective
AbstractHuman breast cancer is a heterogeneous disease with numerous subtypes that have been defined through immunohistological, histological, and gene expression patterns. The diversity of breast cancer has made the study of its various underlying causes complex. To facilitate the examination of particular facets of breast cancer, mouse models have been generated, ranging from carcinogen induced models to genetically engineered mice. While mouse models have been generated to mimic the initiating event, including p53 loss, BRCA loss, or overexpression of HER2 / Neu / erbB2, other genomic events are often not well character...
Source: Journal of Mammary Gland Biology and Neoplasia - June 20, 2019 Category: Cancer & Oncology Source Type: research

GATA3 Truncating Mutations Promote Cistromic Re-Programming In Vitro, but Not Mammary Tumor Formation in Mice
AbstractHeterozygous mutations in the transcription factor GATA3 are identified in 10 –15% of all breast cancer cases. Most of these are protein-truncating mutations, concentrated within or downstream of the second GATA-type zinc-finger domain. Here, we investigated the functional consequences of expression of two truncated GATA3 mutants, in vitro in breast cancer cell lines and in vivo in the mouse mammary gland. We found that the truncated GATA3 mutants display altered DNA binding activity caused by preferred tethering through FOXA1. In addition, expression of the truncated GATA3 mutants reduces E-cadherin expressi...
Source: Journal of Mammary Gland Biology and Neoplasia - June 18, 2019 Category: Cancer & Oncology Source Type: research

BRCA1 Attenuates Progesterone Effects on Proliferation and NF κB Activation in Normal Human Mammary Epithelial Cells
This study investigates the effect of reduced BRCA1 expression on proliferation and NFκB activation in human breast cells, and the impact of progesterone on these effects. The major findings are that: 1) Reduced BRCA1 levels inhibit cell growth in normal human mammary cells and breast cancer cells; 2) Reduced BRCA1 levels stimulated i nflammatory targets and NFκB activity in normal human mammary cells; 3) Wildtype BRCA1 inhibited the pro-proliferative effects of progesterone in normal mammary epithelial cells, and; 4) Progesterone attenuated BRCA1-mediated NFκB activation in normal human mammary cells. Th...
Source: Journal of Mammary Gland Biology and Neoplasia - May 17, 2019 Category: Cancer & Oncology Source Type: research

Emerging Role of SOX Proteins in Breast Cancer Development and Maintenance
AbstractTheSOX genes encode a family of more than 20 transcription factors that are critical regulators of embryogenesis and developmental processes and, when aberrantly expressed, have been shown to contribute to tumor development and progression in both an oncogenic and tumor suppressive role. Increasing evidence demonstrates that the SOX proteins play essential roles in multiple cellular processes that mediate or contribute to oncogenic transformation and tumor progression. In the context of breast cancer, SOX proteins function both as oncogenes and tumor suppressors and have been shown to be associated with tumor stage...
Source: Journal of Mammary Gland Biology and Neoplasia - May 8, 2019 Category: Cancer & Oncology Source Type: research

Metformin and Breast Cancer: Molecular Targets
AbstractMetformin has been the first-line drug for the treatment of type II diabetes mellitus for decades, being presently the most widely prescribed antihyperglycemic drug. Retrospective studies associate the use of metformin with a reduction in cancer incidence and cancer-related death. However, despite extensive research about the molecular effects of metformin in cancer cells, its mode of action remains controversial. The major molecular targets of metformin include complex I of the mitochondrial electron transport chain, adenosine monophosphate (AMP)-activated protein kinase (AMPK), and mechanistic target of rapamycin...
Source: Journal of Mammary Gland Biology and Neoplasia - March 21, 2019 Category: Cancer & Oncology Source Type: research

A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials
AbstractIn order to develop a practical model of breast cancer, with in vitro and syngeneic,  immune-intact, in vivo growth capacity, we established a primary cell line derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2*)NDL2-5Mul mouse, referred to as “NDLUCD”. The cell line is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. NDLUCD tumors in FVB/N mice exhibit high expression ofErbB2 andErbB3 and signaling molecules downstream ofErbB2. Th...
Source: Journal of Mammary Gland Biology and Neoplasia - February 27, 2019 Category: Cancer & Oncology Source Type: research

Inhibition of Tumor Progression by N G -Nitro-L-arginine Methyl Ester in 7,12- dimethylbenz(a)anthracene Induced Breast Cancer: Nitric Oxide Synthase Inhibition as an Antitumor Prevention
AbstractBreast cancer has high mortality rates among the women in the Republic of Armenia. It is now evident that nitric oxide plays important roles in various stages of carcinogenesis such as oncogene activation, tumor suppressor genes, modulation of apoptosis and metastasis. Advances in our understanding of the metabolism and molecular functions of arginine alterations in cancer have led to resurgence in the interest of targeting arginine catabolism, as an anticancer strategy. NOS inhibitors have been proposed, as a way to treat cancer. We have been researching the anti-tumor potential of the NOS inhibition by NG-Nitro-L...
Source: Journal of Mammary Gland Biology and Neoplasia - February 26, 2019 Category: Cancer & Oncology Source Type: research

RETRACTED ARTICLE: Inhibition of Tumor Progression by N G -Nitro-L-arginine Methyl Ester in 7,12- dimethylbenz(a)anthracene Induced Breast Cancer: Nitric Oxide Synthase Inhibition as an Antitumor Prevention
(Source: Journal of Mammary Gland Biology and Neoplasia)
Source: Journal of Mammary Gland Biology and Neoplasia - February 25, 2019 Category: Cancer & Oncology Source Type: research