In Vitro Models for Studying Invasive Transitions of Ductal Carcinoma In Situ
AbstractAbout one fourth of all newly identified cases of breast carcinoma are diagnoses of breast ductal carcinoma in situ (DCIS). Since we cannot yet distinguish DCIS cases that would remain indolent from those that may progress to life-threatening invasive ductal carcinoma (IDC), almost all women undergo aggressive treatment. In order to allow for more rational individualized treatment, we and others are developing in vitro models to identify and validate druggable pathways that mediate the transition of DCIS to IDC. These models range from conventional two-dimensional (2D) monolayer cultures on plastic to 3D cultures i...
Source: Journal of Mammary Gland Biology and Neoplasia - July 28, 2018 Category: Cancer & Oncology Source Type: research

Pax-5 Inhibits NF- κB Activity in Breast Cancer Cells Through IKKε and miRNA-155 Effectors
In this study, we set out to elucidate the regulatory network between differentialPax-5 expression and NF- κB activity which dictate breast cancer malignancy. Through next-generation sequencing (NGS) of breast cancer cells conditionally expressingPax-5, we profile significantly upregulated microRNAs; including microRNA-155, a known regulator of pathological processes and suppressor of malignant growth. Through the conditional expression of microRNA-155 in breast cancer models, we identify and validate IKK ε (IKBKE) as a downstream target and an essential effector ofPax-5-mediated suppression of NF- κB signaling. Using r...
Source: Journal of Mammary Gland Biology and Neoplasia - July 21, 2018 Category: Cancer & Oncology Source Type: research

Polarized Secretion of Extracellular Vesicles by Mammary Epithelia
AbstractExtracellular vesicles (EVs) are secreted by many cell types and are increasingly investigated for their role in human diseases including cancer. Here we focus on the secretion and potential physiological function of non-pathological EVs secreted by polarized normal mammary epithelial cells. Using a transwell system to allow formation of epithelial polarity and EV collection from the apical versus basolateral compartments, we found that impaired secretion of EVs by knockdown of RAB27A or RAB27B suppressed the establishment of mammary epithelial polarity, and that addition of apical but not basolateral EVs suppresse...
Source: Journal of Mammary Gland Biology and Neoplasia - July 3, 2018 Category: Cancer & Oncology Source Type: research

Histology and Transcriptome Profiles of the Mammary Gland across Critical Windows of Development in Sprague Dawley Rats
We examined mammary glands in femal e Sprague Dawley rats across six developmental stages – pre-pubertal, peri-pubertal, pubertal, lactation, adult parous and adult nulliparous. We investigated histology by Hematoxylin and Eosin and Mallory’s Trichrome stain, proliferative and apoptotic rate by immunohistochemistry and whole-trans criptome by microarrays. We identified differentially expressed genes between adjacent developmental stages by linear models, underlying pathways by gene ontology analysis and gene networks and hubs active across developmental stages by coexpression network analysis. Mammary gland development...
Source: Journal of Mammary Gland Biology and Neoplasia - June 28, 2018 Category: Cancer & Oncology Source Type: research

Oxytocin Induces Mammary Epithelium Disruption and Could Stimulate Epithelial Cell Exfoliation
AbstractMammary epithelial cells (MEC) are exfoliated from the epithelium into milk, influencing the number of MEC present in the udder. This process is associated with epithelium integrity. The release of oxytocin (OT) induced by milking causes myoepithelial cell contraction, which, in turn, may stimulate MEC exfoliation through mechanical forces. To investigate the role of OT in MEC exfoliation, we inhibited or induced myoepithelial cell contraction by injecting the OT receptor antagonist atosiban (Ato) or a supraphysiological dose of OT, respectively. Eight cows were assigned to 2 treatments during 2 milkings according ...
Source: Journal of Mammary Gland Biology and Neoplasia - June 8, 2018 Category: Cancer & Oncology Source Type: research

cIAP2 Is an Independent Signaling and Survival Factor during Mammary Lactational Involution and Tumorigenesis
AbstractCellular inhibitor of apoptosis proteins-1 and -2 (cIAP1/2) are integral to regulation of apoptosis and signaling by the tumor necrosis factor (TNF) and related family of receptors. The expression of cIAP2 in tissues is typically low and considered functionally redundant with cIAP1, however cIAP2 can be activated by a variety of cellular stresses. Members of the TNFR family and their ligands have essential roles in mammary gland biology. We have found thatcIAP2−/− virgin mammary glands have reduced ductal branching and delayed lobuloalveogenesis in early pregnancy. Post-lactational involution involves two phase...
Source: Journal of Mammary Gland Biology and Neoplasia - June 6, 2018 Category: Cancer & Oncology Source Type: research

Psychosocial Stress Exposure Disrupts Mammary Gland Development
AbstractExposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8 –25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially s...
Source: Journal of Mammary Gland Biology and Neoplasia - June 1, 2018 Category: Cancer & Oncology Source Type: research

Does the Mouse Mammary Gland Arise from Unipotent or Multipotent Mammary Stem/Progenitor Cells?
AbstractThe presence of long-lived lineage restricted progenitor and multipotent progenitor cells in adult mouse mammary gland for cancer development is compelling. Mammary cancers are phenotypically diverse This might be explained by transformation of long-lived, lineage-limited progenitor subpopulations. Mammary multipotent epithelial stem cells and their environmental niches must be considered, since their niche(s), once empty might be occupied by lineage-limited progenitors that are proximal. The existence of premalignant mammary populationst that manifest characteristics of lineage limitation argues strongly for this ...
Source: Journal of Mammary Gland Biology and Neoplasia - June 1, 2018 Category: Cancer & Oncology Source Type: research

Attenuation of Mammary Gland Dysplasia and Feeding Difficulties in Tabby Mice by Fetal Therapy
AbstractHypohidrotic ectodermal dysplasias (HED) are hereditary differentiation disorders of multiple ectodermal structures including the mammary gland. The X-linked form of HED (XLHED) is caused by a lack of the secreted signaling molecule ectodysplasin A1 (EDA1) which is encoded by the geneEDA and belongs to the tumor necrosis factor (TNF) superfamily. Although male patients (hemizygous) are usually more severely affected by XLHED, heterozygous female carriers of anEDA mutation may also suffer from a variety of symptoms, in particular from abnormal development of their breasts. InTabby mice, a well-studied animal model o...
Source: Journal of Mammary Gland Biology and Neoplasia - June 1, 2018 Category: Cancer & Oncology Source Type: research

Can Bovine Leukemia Virus Be Related to Human Breast Cancer? A Review of the Evidence
We present a compilation of the current knowledge on the subject and some prospective analysis that is required to fully end this controversy. (Source: Journal of Mammary Gland Biology and Neoplasia)
Source: Journal of Mammary Gland Biology and Neoplasia - May 18, 2018 Category: Cancer & Oncology Source Type: research

Radiological, Histological and Chemical Analysis of Breast Microcalcifications: Diagnostic Value and Biological Significance
AbstractClassification of mammary microcalcifications is based on radiological and histological characteristics that are routinely evaluated during the diagnostic path for the identification of breast cancer, or in patients at risk of developing breast cancer. The main aim of this study was to explore the relationship between the imaging parameters most commonly used for the study of mammary microcalcifications and the corresponding histological and chemical properties. To this end, we matched the radiographic characteristics of microcalcifications to breast lesion type, histology of microcalcifications and elemental compo...
Source: Journal of Mammary Gland Biology and Neoplasia - May 9, 2018 Category: Cancer & Oncology Source Type: research

The Mammary Microenvironment in Mastitis in Humans, Dairy Ruminants, Rabbits and Rodents: A One Health Focus
AbstractThe One Health concept promotes integrated evaluation of human, animal, and environmental health questions to expedite advances benefiting all species. A recognition of the multi-species impact of mastitis as a painful condition with welfare implications leads us to suggest that mastitis is an ideal target for a One Health approach. In this review, we will evaluate the role of the mammary microenvironment in mastitis in humans, ruminants and rabbits, where appropriate also drawing on studies utilising laboratory animal models. We will examine subclinical mastitis, clinical lactational mastitis, and involution-assoc...
Source: Journal of Mammary Gland Biology and Neoplasia - April 28, 2018 Category: Cancer & Oncology Source Type: research

Psychosocial Stress Exposure Disrupts Mammary Gland Development
AbstractExposure to psychosocial stressors and ensuing stress physiology have been associated with spontaneous invasive mammary tumors in the Sprague-Dawley rat model of human breast cancer. Mammary gland (MG) development is a time when physiologic and environmental exposures influence breast cancer risk. However, the effect of psychosocial stress exposure on MG development remains unknown. Here, in the first comprehensive longitudinal study of MG development in nulliparous female rats (from puberty through young adulthood; 8 –25 wks of age), we quantify the spatial gradient of differentiation within the MG of socially s...
Source: Journal of Mammary Gland Biology and Neoplasia - April 23, 2018 Category: Cancer & Oncology Source Type: research