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Wiley Interdisciplinary Reviews.... 2012The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes.... (Review)
Review
The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial–mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development—pubertal growth, pregnancy, lactation, and involution—occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone (GH) and estrogen, as well as insulin-like growth factor 1 (IGF1), to create a ductal tree that fills the fat pad. Upon pregnancy, the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its prepregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease.
Topics: Animals; Cell Differentiation; Cell Lineage; Female; Hormones; Humans; Mammals; Mammary Glands, Animal; Mammary Glands, Human; Morphogenesis; Stem Cells
PubMed: 22844349
DOI: 10.1002/wdev.35 -
Current Opinion in Cell Biology Oct 2020The mammary gland is a highly dynamic tissue that undergoes repeated cycles of growth and involution during pregnancy and menstruation. It is also the site from which... (Review)
Review
The mammary gland is a highly dynamic tissue that undergoes repeated cycles of growth and involution during pregnancy and menstruation. It is also the site from which breast cancers emerge. Organoids provide an in vitro model that preserves several of the cellular, structural, and microenvironmental features that dictate mammary gland function in vivo and have greatly advanced our understanding of glandular biology. Their tractability for genetic manipulation, live imaging, and high throughput screening have facilitated investigation into the mechanisms of glandular morphogenesis, structural maintenance, tumor progression, and invasion. Opportunities remain to enhance cellular and structural complexity of mammary organoid models, including incorporating additional cell types and hormone signaling.
Topics: Animals; Breast Neoplasms; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Models, Biological; Morphogenesis; Organoids
PubMed: 32535255
DOI: 10.1016/j.ceb.2020.05.003 -
Seminars in Cell & Developmental Biology Jun 2021Embryonic mammary gland development involves the formation of mammary placodes, invagination of flask-shaped mammary buds and development of miniature bi-layered ductal... (Review)
Review
Embryonic mammary gland development involves the formation of mammary placodes, invagination of flask-shaped mammary buds and development of miniature bi-layered ductal trees. Currently there is a good understanding of the factors that contribute to ectodermal cell movements to create these appendages and of pathways that lead to mammary specification and commitment. Gene expression profiles of early bipotent mammary stem cells populations as well as cell surface proteins and transcription factors that promote the emergence of unipotent progenitors have been identified. Analyses of these populations has illuminated not only embryonic mammary development, but highlighted parallel processes in breast cancer. Here we provide an overview of the highly conserved pathways that shape the embryonic mammary gland. Understanding the dynamic signaling events that occur during normal mammary development holds considerable promise to advance attempts to eliminate cancer by restoring differentiative signals.
Topics: Animals; Disease Models, Animal; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Mice
PubMed: 33472760
DOI: 10.1016/j.semcdb.2020.12.012 -
Seminars in Cell & Developmental Biology Jun 2021Our understanding of the molecular events underpinning the development of mammalian organ systems has been increasing rapidly in recent years. With the advent of new and... (Review)
Review
Our understanding of the molecular events underpinning the development of mammalian organ systems has been increasing rapidly in recent years. With the advent of new and improved next-generation sequencing methods, we are now able to dig deeper than ever before into the genomic and epigenomic events that play critical roles in determining the fates of stem and progenitor cells during the development of an embryo into an adult. In this review, we detail and discuss the genes and pathways that are involved in mammary gland development, from embryogenesis, through maturation into an adult gland, to the role of pregnancy signals in directing the terminal maturation of the mammary gland into a milk producing organ that can nurture the offspring. We also provide an overview of the latest research in the single-cell genomics of mammary gland development, which may help us to understand the lineage commitment of mammary stem cells (MaSCs) into luminal or basal epithelial cells that constitute the mammary gland. Finally, we summarize the use of 3D organoid cultures as a model system to study the molecular events during mammary gland development. Our increased investigation of the molecular requirements for normal mammary gland development will advance the discovery of targets to predict breast cancer risk and the development of new breast cancer therapies.
Topics: Animals; Cell Differentiation; Epithelial Cells; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human
PubMed: 33082117
DOI: 10.1016/j.semcdb.2020.09.014 -
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 -
International Journal of Molecular... Dec 2022Breast cancer is among the most common cancers in women, second to skin cancer. Mammary gland development can influence breast cancer development in later life.... (Review)
Review
Breast cancer is among the most common cancers in women, second to skin cancer. Mammary gland development can influence breast cancer development in later life. Processes such as proliferation, invasion, and migration during mammary gland development can often mirror processes found in breast cancer. MicroRNAs (miRNAs), small, non-coding RNAs, can repress post-transcriptional RNA expression and can regulate up to 80% of all genes. Expression of miRNAs play a key role in mammary gland development, and aberrant expression can initiate or promote breast cancer. Here, we review the role of miRNAs in mammary development and breast cancer, and potential parallel roles. A total of 32 miRNAs were found to be expressed in both mammary gland development and breast cancer. These miRNAs are involved in proliferation, metastasis, invasion, and apoptosis in both processes. Some miRNAs were found to have contradictory roles, possibly due to their ability to target many genes at once. Investigation of miRNAs and their role in mammary gland development may inform about their role in breast cancer. In particular, by studying miRNA in development, mechanisms and potential targets for breast cancer treatment may be elucidated.
Topics: Female; Humans; Apoptosis; Breast Neoplasms; Gene Expression Profiling; Mammary Glands, Human; MicroRNAs
PubMed: 36555616
DOI: 10.3390/ijms232415978 -
Journal of Mammary Gland Biology and... Sep 2021Estrogens have pleiotropic effects on many reproductive and non-reproductive tissues and organs including the mammary gland, uterus, ovaries, vagina, and endothelium.... (Review)
Review
Estrogens have pleiotropic effects on many reproductive and non-reproductive tissues and organs including the mammary gland, uterus, ovaries, vagina, and endothelium. Estrogen receptor α functions as the principal mediator of estrogenic action in most of these tissues. Estetrol (E4) is a native fetal estrogen with selective tissue actions that is currently approved for use as the estrogen component in a combined oral contraceptive and is being developed as a menopause hormone therapy (MHT, also known as hormone replacement therapy). However, exogenous hormonal treatments, in particular MHTs, have been shown to promote the growth of preexisting breast cancers and are associated with a variable risk of breast cancer depending on the treatment modality. Therefore, evaluating the safety of E4-based formulations on the breast forms a crucial part of the clinical development process. This review highlights preclinical and clinical studies that have assessed the effects of E4 and E4-progestogen combinations on the mammary gland and breast cancer, focusing in particular on the estrogenic and anti-estrogenic properties of E4. We discuss the potential advantages of E4 over current available estrogen-formulations as a contraceptive and for the treatment of symptoms due to menopause. We also consider the potential of E4 for the treatment of endocrine-resistant breast cancer.
Topics: Breast Neoplasms; Contraceptives, Oral, Hormonal; Estetrol; Female; Hormone Replacement Therapy; Humans; Mammary Glands, Human
PubMed: 34463898
DOI: 10.1007/s10911-021-09497-0 -
Acta Histochemica 2015The aim of this review is to focus on the molecular factors that ensure the optimal development and maintenance of the mammary gland thanks to their integration and... (Review)
Review
The aim of this review is to focus on the molecular factors that ensure the optimal development and maintenance of the mammary gland thanks to their integration and coordination. The development of the mammary gland is supported, not only by endocrine signals, but also by regulatory molecules, which are able to integrate signals from the surrounding microenvironment. A major role is certainly played by homeotic genes, but their incorrect expression during the spatiotemporal regulation of proliferative, functional and differentiation cycles of the mammary gland, may result in the onset of neoplastic processes. Attention is directed also to the endocrine aspects and sexual dimorphism of mammary gland development, as well as the role played by ovarian steroids and their receptors in adult life.
Topics: Adult; Breast Neoplasms; Cell Differentiation; Cell Proliferation; Embryonic Development; Female; Humans; Mammary Glands, Human; Signal Transduction; Stem Cell Niche
PubMed: 25800977
DOI: 10.1016/j.acthis.2015.02.013 -
Development (Cambridge, England) Mar 2015The development of the mammary gland is unique: the final stages of development occur postnatally at puberty under the influence of hormonal cues. Furthermore, during... (Review)
Review
The development of the mammary gland is unique: the final stages of development occur postnatally at puberty under the influence of hormonal cues. Furthermore, during the life of the female, the mammary gland can undergo many rounds of expansion and proliferation. The mammary gland thus provides an excellent model for studying the 'stem/progenitor' cells that allow this repeated expansion and renewal. In this Review, we provide an overview of the different cell types that constitute the mammary gland, and discuss how these cell types arise and differentiate. As cellular differentiation cannot occur without proper signals, we also describe how the tissue microenvironment influences mammary gland development.
Topics: Adipocytes; Animals; Cell Differentiation; Cell Lineage; Epithelial Cells; Female; Fibroblasts; Humans; Mammary Glands, Human; Mice; Puberty; Signal Transduction; Stem Cell Niche; Stem Cells
PubMed: 25758218
DOI: 10.1242/dev.087643 -
Journal of Mammary Gland Biology and... Mar 2021
Topics: Animals; Breast Neoplasms; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Mammary Neoplasms, Animal; Mice; Microscopy; Single-Cell Analysis
PubMed: 34125362
DOI: 10.1007/s10911-021-09492-5