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Journal of Mammary Gland Biology and Neoplasia

Fabiana Lüönd, Ruben Bill, Andrea Vettiger, Heide Oller, Pawel Pelczar, Gerhard Christofori
Genetically engineered mouse models have become an indispensable tool for breast cancer research. Combination of multiple site-specific recombination systems such as Cre/loxP and Flippase (Flp)/Frt allows for engineering of sophisticated, multi-layered conditional mouse models. Here, we report the generation and characterization of a novel transgenic mouse line expressing a mouse codon-optimized Flp under the control of the mouse mammary tumor virus (MMTV) promoter. These mice show robust Flp-mediated recombination in luminal mammary gland and breast cancer cells but no Flp activity in non-mammary tissues, with the exception of limited activity in salivary glands...
September 12, 2018: Journal of Mammary Gland Biology and Neoplasia
Michelle S Han, Seema A Khan
Ductal carcinoma in situ (DCIS) of the breast is a non-obligatory precursor to invasive breast carcinoma, with a variable natural history and biological potential for progression to invasive disease. Over the past 30 years, clinical trials have applied the therapeutic principles used for invasive carcinoma to treat DCIS (surgery, with or without breast radiotherapy, and post-operative endocrine therapy), with excellent survival outcomes, and in-breast recurrence rates that range from 0.5 to 1% annually. However, half of such recurrences are again in-situ lesions, and intensive therapy is likely not necessary for all patients...
September 11, 2018: Journal of Mammary Gland Biology and Neoplasia
Sabreen F Fostok, Mirvat El-Sibai, Marwan El-Sabban, Rabih S Talhouk
Connexins (Cxs), the building blocks of gap junctions (GJs), exhibit spatiotemporal patterns of expression and regulate the development and differentiation of the mammary gland, acting via channel-dependent and channel-independent mechanisms. Impaired Cx expression and localization are reported in breast cancer, suggesting a tumor suppressive role for Cxs. The signaling events that mediate the role of GJs in the development and tumorigenesis of the mammary gland remain poorly identified. The Wnt pathways, encompassing the canonical or the Wnt/β-catenin pathway and the noncanonical β-catenin-independent pathway, also play important roles in those processes...
September 7, 2018: Journal of Mammary Gland Biology and Neoplasia
Vidya C Sinha, Helen Piwnica-Worms
Ductal carcinoma in situ (DCIS) is a non-invasive proliferative growth in the breast that serves as a non-obligate precursor to invasive ductal carcinoma. The widespread adoption of screening mammography has led to a steep increase in the detection of DCIS, which now comprises approximately 20% of new breast cancer diagnoses in the United States. Interestingly, the intratumoral heterogeneity (ITH) that has been observed in invasive breast cancers may have been established early in tumorigenesis, given the vast and varied ITH that has been detected in DCIS...
September 7, 2018: Journal of Mammary Gland Biology and Neoplasia
Andrew C Nelson, Heather L Machado, Kathryn L Schwertfeger
Refinements in early detection, surgical and radiation therapy, and hormone receptor-targeted treatments have improved the survival rates for breast cancer patients. However, the ability to reliably identify which non-invasive lesions and localized tumors have the ability to progress and/or metastasize remains a major unmet need in the field. The current diagnostic and therapeutic strategies focus on intrinsic alterations within carcinoma cells that are closely associated with proliferation. However, substantial accumulating evidence has indicated that permissive changes in the stromal tissues surrounding the carcinoma play an integral role in breast cancer tumor initiation and progression...
August 31, 2018: Journal of Mammary Gland Biology and Neoplasia
Fariba Behbod, Angelica M Gomes, Heather L Machado
Breast cancer development is a multi-step process in which genetic and molecular heterogeneity occurs at multiple stages. Ductal carcinoma arises from pre-invasive lesions such as atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), which progress to invasive and metastatic cancer. The feasibility of obtaining tissue samples from all stages of progression from the same patient is low, and thus molecular studies dissecting the mechanisms that mediate the transition from pre-invasive DCIS to invasive carcinoma have been hampered...
August 25, 2018: Journal of Mammary Gland Biology and Neoplasia
Gerard A Tarulli, Geraldine Laven-Law, Mona Shehata, Kirsty A Walters, Iza M Denis, Md Mostafizur Rahman, David J Handelsman, Nicola R Dean, Wayne D Tilley, Theresa E Hickey
Androgens influence mammary gland development but the specific role of the androgen receptor (AR) in mammary function is largely unknown. We identified cell subsets that express AR in vivo and determined the effect of AR activation and transgenic AR inhibition on sub-populations of the normal mouse mammary epithelium by flow cytometry and immunohistochemistry. Immunolocalisation of AR with markers of lineage identity was also performed in human breast tissues. AR activation in vivo significantly decreased the proportion of basal cells, and caused an accumulation of cells that expressed a basal cell marker but exhibited morphological features of luminal identity...
August 12, 2018: Journal of Mammary Gland Biology and Neoplasia
Shira Bernard, Megan Myers, Wei Bin Fang, Brandon Zinda, Curtis Smart, Diana Lambert, An Zou, Fang Fan, Nikki Cheng
With improved screening methods, the numbers of abnormal breast lesions diagnosed in women have been increasing over time. However, it remains unclear whether these breast lesions will develop into invasive cancers. To more effectively predict the outcome of breast lesions and determine a more appropriate course of treatment, it is important to understand the underlying mechanisms that regulate progression of non-invasive lesions to invasive breast cancers. A hallmark of invasive breast cancers is the accumulation of fibroblasts...
August 9, 2018: Journal of Mammary Gland Biology and Neoplasia
Xiaoyu Hu, Naisheng Zhang, Yunhe Fu
Mastitis is important disease that causes huge economic losses in the dairy industry. In recent years, antibiotic therapy has become the primary treatment for mastitis, however, due to drug residue in milk and food safety factors, we lack safe and effective drugs for treating mastitis. Therefore, new targets and drugs are urgently needed to control mastitis. LXRα, one of the main members of the nuclear receptor superfamily, is reported to play important roles in metabolism, infection and immunity. Activation of LXRα could inhibit LPS-induced mastitis...
July 31, 2018: Journal of Mammary Gland Biology and Neoplasia
Ethan J Brock, Kyungmin Ji, Seema Shah, Raymond R Mattingly, Bonnie F Sloane
About 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...
July 28, 2018: Journal of Mammary Gland Biology and Neoplasia
Jason Harquail, Nicolas LeBlanc, Carine Landry, Nicolas Crapoulet, Gilles A Robichaud
Pax-5, an essential transcription factor in B cell development, is aberrantly expressed in various B cell cancer lesions and solid tumors such as breast carcinoma. We have recently shown that Pax-5 regulates NF-κB activity which lead to the modulation of breast cancer phenotypic features (EMT-MET). NF-κB is known as a central mediator in inflammation, stress response as well as being a gatekeeper of pro-tumorigenic activity. However, little is known as to how Pax-5 affects this modulation. We thus turned our attention to microRNAs as potential regulatory effectors...
September 2018: Journal of Mammary Gland Biology and Neoplasia
Andrew R Chin, Wei Yan, Minghui Cao, Xuxiang Liu, Shizhen Emily Wang
Extracellular 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 suppressed epithelial polarity in a dose-dependent manner...
September 2018: Journal of Mammary Gland Biology and Neoplasia
Kalpana Gopalakrishnan, Susan L Teitelbaum, James Wetmur, Fabiana Manservisi, Laura Falcioni, Simona Panzacchi, Federica Gnudi, Fiorella Belpoggi, Jia Chen
Breast development occurs through well-defined stages representing 'windows of susceptibility' to adverse environmental exposures that potentially modify breast cancer risk. Systematic characterization of morphology and transcriptome during normal breast development lays the foundation of our understanding of cancer etiology. We examined mammary glands in female 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-transcriptome by microarrays...
September 2018: Journal of Mammary Gland Biology and Neoplasia
L Herve, V Lollivier, H Quesnel, Marion Boutinaud
Mammary 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...
September 2018: Journal of Mammary Gland Biology and Neoplasia
David Carr, Rosanna Lau, Alexandra D Hnatykiw, Gwendoline C D Ward, Manijeh Daneshmand, Miguel A Cabrita, M A Christine Pratt
Cellular 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 that cIAP2-/- virgin mammary glands have reduced ductal branching and delayed lobuloalveogenesis in early pregnancy...
September 2018: Journal of Mammary Gland Biology and Neoplasia
Mandy Wahlbuhl, Sonia Schuepbach-Mallepell, Christine Kowalczyk-Quintas, Angela Dick, Fabian B Fahlbusch, Pascal Schneider, Holm Schneider
Hypohidrotic 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 gene EDA and belongs to the tumor necrosis factor (TNF) superfamily. Although male patients (hemizygous) are usually more severely affected by XLHED, heterozygous female carriers of an EDA mutation may also suffer from a variety of symptoms, in particular from abnormal development of their breasts...
September 2018: Journal of Mammary Gland Biology and Neoplasia
Lucia Martinez Cuesta, Pamela Anahi Lendez, Maria Victoria Nieto Farias, Guillermina Laura Dolcini, Maria Carolina Ceriani
The incidence of breast cancer is continuously increasing worldwide, as influenced by many factors that act synergistically. In the last decade there was an increasing interest in the possible viral etiology of human breast cancer. Since then, many viruses have been associated with this disease (murine mammary tumor virus, MMTV; Epstein-Barr virus, EBV; and human papillomavirus, HPV). Recently, BLV has been identified in human breast cancers giving rise to the hypothesis that it could be one of the causative agents of this condition...
September 2018: Journal of Mammary Gland Biology and Neoplasia
Katherine Hughes, Christine J Watson
The 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...
June 2018: Journal of Mammary Gland Biology and Neoplasia
Marianna B Johnson, Joscelyn N Hoffmann, Hannah M You, Ricardo R Lastra, Sully Fernandez, Jordan W Strober, Ahmad B Allaw, Matthew J Brady, Suzanne D Conzen, Martha K McClintock
Exposure 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 stressed (isolated) and control (grouped) rats...
June 2018: Journal of Mammary Gland Biology and Neoplasia
Gilbert H Smith, Daniel Medina
The 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 proposition...
June 2018: Journal of Mammary Gland Biology and Neoplasia
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