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Cellular and Molecular Life Sciences :... Dec 2007During its lifetime, the mammary gland undergoes many phases of development and differentiation. Much of this occurs during puberty, when the ductal epithelium expands... (Review)
Review
During its lifetime, the mammary gland undergoes many phases of development and differentiation. Much of this occurs during puberty, when the ductal epithelium expands by branching morphogenesis, invading the surrounding fat pad to form an organised mammary tree. Throughout its existence, the epithelium will go through several cycles of proliferation and cell death during pregnancy, lactation and involution. Many of the signalling mechanisms which control the initial invasion of the fat pad by the epithelium, and regulate its continuing plasticity, can be harnessed or corrupted by tumour cells in order to support their aberrant growth and progression towards invasion. This is true not just for the epithelial cells themselves but also for cells in the surrounding microenvironment, including fibroblasts, macrophages and adipocytes. This review examines the complex web of signalling and adhesion interactions controlling branching morphogenesis, and how their alteration can promote malignancy. Current in vivo and in vitro mammary gland models are also discussed. (Part of a Multi-author Review).
Topics: Animals; Breast Neoplasms; Cell Adhesion; Epidermal Growth Factor; Humans; Mammary Glands, Animal; Mammary Glands, Human; Matrix Metalloproteinases; Models, Biological; Neoplasm Invasiveness; Oncogene Proteins v-erbB; Stem Cells; Transcription Factors; Transforming Growth Factor beta
PubMed: 17955178
DOI: 10.1007/s00018-007-7386-2 -
Seminars in Cell & Developmental Biology Jun 2021Understanding the complexity and heterogeneity of mammary cell subpopulations is vital to delineate the mechanisms behind breast cancer development, progression and... (Review)
Review
Understanding the complexity and heterogeneity of mammary cell subpopulations is vital to delineate the mechanisms behind breast cancer development, progression and prevention. Increasingly sophisticated tools for investigating these cell subtypes has led to the development of a greater understanding of these cell subtypes, complex interplay of certain subtypes and their developmental potential. Of note, increasing accessibility and affordability of single cell technologies has led to a plethora of studies being published containing data from mammary cell subtypes and their differentiation potential in both mice and human data sets. Here, we review the different types of single cell technologies and how they have been used to improve our understanding of mammary gland development.
Topics: Female; Humans; Mammary Glands, Human; Single-Cell Analysis
PubMed: 33810979
DOI: 10.1016/j.semcdb.2021.03.013 -
Proceedings of the National Academy of... Mar 2022SignificanceBisphenol A (BPA), found in many plastic products, has weak estrogenic effects that can be harmful to human health. Thus, structurally related...
SignificanceBisphenol A (BPA), found in many plastic products, has weak estrogenic effects that can be harmful to human health. Thus, structurally related replacements-bisphenol S (BPS) and bisphenol F (BPF)-are coming into wider use with very few data about their biological activities. Here, we compared the effects of BPA, BPS, and BPF on human mammary organoids established from normal breast tissue. BPS disrupted organoid architecture and induced supernumerary branching. At a proteomic level, the bisphenols altered the abundance of common targets and those that were unique to each compound. The latter included proteins linked to tumor-promoting processes. These data highlighted the importance of testing the human health effects of replacements that are structurally related to chemicals of concern.
Topics: Benzhydryl Compounds; Carcinogenesis; Estrogens; Humans; Mammary Glands, Human; Organoids; Phenols; Proteome; Proteomics; Sulfones
PubMed: 35263230
DOI: 10.1073/pnas.2115308119 -
Journal of Mammary Gland Biology and... Jun 2015The mammary gland undergoes dramatic post-natal growth beginning at puberty, followed by full development occurring during pregnancy and lactation. Following lactation,... (Review)
Review
The mammary gland undergoes dramatic post-natal growth beginning at puberty, followed by full development occurring during pregnancy and lactation. Following lactation, the alveoli undergo apoptosis, and the mammary gland reverses back to resemble the nonparous gland. This process of growth and regression occurs for multiple pregnancies, suggesting the presence of a hierarchy of stem and progenitor cells that are able to regenerate specialized populations of mammary epithelial cells. Expansion of epithelial cell populations in the mammary gland is regulated by ovarian steroids, in particular estrogen acting through its receptor estrogen receptor alpha (ERα) and progesterone signaling through progesterone receptor (PR). A diverse number of stem and progenitor cells have been identified based on expression of cell surface markers and functional assays. Here we review the current understanding of how estrogen and progesterone act together and separately to regulate stem and progenitor cells within the human and mouse mammary tissues. Better understanding of the hierarchal organization of epithelial cell populations in the mammary gland and how the hormonal milieu affects its regulation may provide important insights into the origins of different subtypes of breast cancer.
Topics: Aging; Animals; Cell Differentiation; Epithelium; Estrogen Receptor alpha; Estrogens; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Parity; Pregnancy; Progesterone; Receptors, Progesterone; Stem Cells; Transcription Factors
PubMed: 26188694
DOI: 10.1007/s10911-015-9337-0 -
Alternative Therapies in Health and... Sep 2023Mammary gland hyperplasia is a common gynecological disease, which seriously affects the patient's physical and mental health. Therapeutic strategies to treat the... (Review)
Review
OBJECTIVE
Mammary gland hyperplasia is a common gynecological disease, which seriously affects the patient's physical and mental health. Therapeutic strategies to treat the disease include endocrine therapy and surgery. Compared to Western treatment, traditional Chinese medicine prescription shows its superiority in treatment. The purpose of this review was to provide a reference for the determination of the pathogenesis, treatment principles, and treatment methods of mammary gland hyperplasia.
METHOD
This article comprehensively reviewed the records on mammary gland hyperplasia in ancient Chinese medical literature.
RESULTS
The present review discussed the disease and summarizes the information on mammary gland hyperplasia, including the disease name, the traditional Chinese medicine analysis, etiology, pathogenesis, treatment methods, prognosis, and nursing care.
CONCLUSION
We clearly described the research history of mammary gland hyperplasia, and the analysis and treatment of this disease by physicians in past dynasties. This information will help modern physicians to fully understand the disease development and treatment process.
Topics: Humans; Hyperplasia; Mammary Glands, Human; Medicine, Chinese Traditional
PubMed: 37235489
DOI: No ID Found -
Nature Communications Sep 2018Adipocytes undergo pronounced changes in size and behavior to support diverse tissue functions, but the mechanisms that control these changes are not well understood....
Adipocytes undergo pronounced changes in size and behavior to support diverse tissue functions, but the mechanisms that control these changes are not well understood. Mammary gland-associated white adipose tissue (mgWAT) regresses in support of milk fat production during lactation and expands during the subsequent involution of milk-producing epithelial cells, providing one of the most marked physiological examples of adipose growth. We examined cellular mechanisms and functional implications of adipocyte and lipid dynamics in the mouse mammary gland (MG). Using in vivo analysis of adipocyte precursors and genetic tracing of mature adipocytes, we find mature adipocyte hypertrophy to be a primary mechanism of mgWAT expansion during involution. Lipid tracking and lipidomics demonstrate that adipocytes fill with epithelial-derived milk lipid. Furthermore, ablation of mgWAT during involution reveals an essential role for adipocytes in milk trafficking from, and proper restructuring of, the mammary epithelium. This work advances our understanding of MG remodeling and tissue-specific roles for adipocytes.
Topics: Adipocytes; Adipocytes, White; Animals; Breast Feeding; Cell Size; Epithelial Cells; Fatty Acids; Female; Humans; Lactation; Lipid Metabolism; Mammary Glands, Animal; Mammary Glands, Human; Mice, Inbred C57BL; Mice, Transgenic; Pregnancy
PubMed: 30181538
DOI: 10.1038/s41467-018-05911-0 -
Cold Spring Harbor Perspectives in... Sep 2010DNA methylation and histone modifications have essential roles in remodeling chromatin structure of genes necessary for multi-lineage differentiation of mammary... (Review)
Review
DNA methylation and histone modifications have essential roles in remodeling chromatin structure of genes necessary for multi-lineage differentiation of mammary stem/progenitor cells. The role of this well-defined epigenetic programming is to heritably maintain transcriptional plasticity of these loci over multiple cell divisions in the differentiated progeny. Epigenetic events can be deregulated in progenitor cells chronically exposed to xenoestrogen or inflammatory microenvironment. In addition, epigenetically mediated silencing of genes associated with tumor suppression can take place, resulting in clonal proliferation of undifferentiated or semidifferentiated cells. Alternatively, microRNAs that negatively regulate the expression of their protein-coding targets may become epigenetically repressed, leading to oncogenic expression of these genes. Here we further discuss interactions between DNA methylation and histone modifications that have significant contributions to the differentiation of mammary stem/progenitor cells and to tumor initiation and progression.
Topics: Breast Neoplasms; Cell Differentiation; Cell Transformation, Neoplastic; Chromatin Assembly and Disassembly; DNA Methylation; Epigenesis, Genetic; Female; Humans; Mammary Glands, Human; Stem Cells
PubMed: 20610549
DOI: 10.1101/cshperspect.a004515 -
Cell Proliferation Oct 2003Significant advances in the stem-cell biology of several tissues, including the mammary gland, have occurred over the past several years. Recent progress on stem-cell... (Review)
Review
Significant advances in the stem-cell biology of several tissues, including the mammary gland, have occurred over the past several years. Recent progress on stem-cell fate determination, molecular markers, signalling pathways and niche interactions in haematopoietic, neuronal and muscle tissue may provide parallel insight into the biology of mammary epithelial stem cells. Taking advantage of approaches similar to those employed to isolate and characterize haematopoietic and epidermal stem cells, we have identified a mammary epithelial cell population with several stem/progenitor cell qualities. In this article, we review some recent data on mammary epithelial stem/progenitor cells in genetically engineered mouse models. We also discuss several potential molecular markers, including stem-cell antigen-1 (Sca-1), which may be useful for both the isolation of functional mammary epithelial stem/progenitor cells and the analysis of tumour aetiology and phenotype in genetically engineered mouse models. In different transgenic mammary tumour models, Sca-1 expression levels, as well as several other putative markers of progenitors including keratin-6, possess dramatically altered expression profiles. These data suggest that the heterogeneity of mouse models of breast cancer may partially reflect the selection or expansion of different progenitors.
Topics: Animals; Cell Separation; Humans; Mammary Glands, Animal; Mammary Glands, Human; Stem Cells
PubMed: 14521513
DOI: 10.1046/j.1365-2184.36.s.1.3.x -
International Journal of Molecular... Sep 2017Environmental exposure to estrogens and estrogen like contaminants during early development is thought to contribute to the risk of developing breast cancer primarily...
Environmental exposure to estrogens and estrogen like contaminants during early development is thought to contribute to the risk of developing breast cancer primarily due to an early onset of puberty; however, exposure during key developing windows may also influence the risk of developing the disease. The goal of this study was to ask whether exposure to the metalloestrogen cadmium alters mammary gland development due to acceleration of puberty onset or to an effect on early development of the mammary gland. The results show that, in addition to advancing the onset of puberty, exposure to the metalloestrogen cadmium altered mammary gland development prior to its effect on puberty onset. exposure resulted in an expansion of the number of mammosphere-forming cells in the neonatal mammary gland and an increase in branching, epithelial cells, and density in the prepubertal mammary gland. In the postpubertal mammary gland, there was a further expansion of the mammary stem/progenitor cell population and overexpression of estrogen receptor-alpha (ERα) that was due to the overexpression and altered regulation of the ERα transcripts derived from exons O and OT in response to estradiol. These results suggest that exposure to cadmium increases stem/progenitor cells, cell density, and expression of estrogen receptor-alpha that may contribute to the risk of developing breast cancer.
Topics: Animals; Cadmium; Cells, Cultured; Epithelial Cells; Estrogen Receptor alpha; Female; Humans; Mammary Glands, Human; Maternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Stem Cells
PubMed: 28891935
DOI: 10.3390/ijms18091939 -
Journal of Mammary Gland Biology and... Jun 2022Breast cancers in humans belong to one of several intrinsic molecular subtypes each with different tumor biology and different clinical impact. Mammary gland tumors in...
Breast cancers in humans belong to one of several intrinsic molecular subtypes each with different tumor biology and different clinical impact. Mammary gland tumors in dogs are proposed as a relevant comparative model for human breast cancer; however, it is still unclear whether the intrinsic molecular subtypes have the same significance in dogs and humans. Using publicly available data, we analyzed gene expression and whole-exome sequencing data from 158 canine mammary gland tumors. We performed molecular subtyping using the PAM50 method followed by subtype-specific comparisons of gene expression characteristics, mutation patterns and copy number profiles between canine tumors and human breast tumors from The Cancer Genome Atlas (TCGA) breast cancer cohort (n = 1097). We found that luminal A canine tumors greatly resemble luminal A human tumors both in gene expression characteristics, mutations and copy number profiles. Also, the basal-like canine and human tumors were relatively similar, with low expression of luminal epithelial markers and high expression of genes involved in cell proliferation. There were, however, distinct differences in immune-related gene expression patterns in basal-like tumors between the two species. Characteristic HER2-enriched and luminal B subtypes were not present in the canine cohort, and we found no tumors with high-level ERBB2 amplifications. Benign and malignant canine tumors displayed similar PAM50 subtype characteristics. Our findings indicate that deeper understanding of the different molecular subtypes in canine mammary gland tumors will further improve the value of canines as comparative models for human breast cancer.
Topics: Animals; Biomarkers, Tumor; Breast Neoplasms; Cohort Studies; Dogs; Female; Gene Expression Regulation, Neoplastic; Humans; Mammary Glands, Human; Mammary Neoplasms, Animal
PubMed: 35932380
DOI: 10.1007/s10911-022-09523-9