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 <  0.01). OS tumors grow significantly faster than SQ tumors. Similarly, OS tumors demonstrated significantly more mitotic figures and Ki-67 positive cells than SQ tumors. The tumor re-transplantation rate significantly increased by the second and third generations with the OS method. The time from implantation to development of a palpable tumor dramatically decreased after the first passage. PDX of ER(+) tumors demonstrated sig...
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 stoichiometry relative to ...
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 compa...
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 mammary epithelial cells (MME...
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