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International Journal of Molecular... Oct 2016The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at... (Review)
Review
The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women. Breast cancer spreads to the bone in approximately 70% of cases with advanced breast cancer. Despite treatment, new bone metastases will still occur in 30%-50% of patients. Only 20% of patients with bone metastases survive five years after the diagnosis of bone metastasis. The breast cancer cells in the bone microenvironment release soluble factors that engage osteoclasts and/or osteoblasts and result in bone breakdown. The breakdown of the bone matrix, in turn, enhances the proliferation of the cancer cells, creating a vicious cycle. Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins. Interestingly, prolactin has the potential to affect multiple proteins that are involved in both breast development and likely bone metastasis, as well. Prolactin has normal bone homeostatic roles and, combined with the natural "recycling" of proteins in different tissues that can be used for breast development and function, or in bone function, increases the impact of prolactin signaling in breast cancer bone metastases. Thus, this review will focus on the role of prolactin in breast development, bone homeostasis and in breast cancer to bone metastases, covering the molecular aspects of the vicious cycle.
Topics: Bone Neoplasms; Bone and Bones; Breast Neoplasms; Female; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Humans; Mammary Glands, Human; Neoplastic Cells, Circulating; Osteoblasts; Osteoclasts; Osteolysis; Prolactin; Receptors, Prolactin; Signal Transduction
PubMed: 27782069
DOI: 10.3390/ijms17101764 -
Cold Spring Harbor Perspectives in... Oct 2010The mammary gland is an organ that at once gives life to the young, but at the same time poses one of the greatest threats to the mother. Understanding how the tissue... (Review)
Review
The mammary gland is an organ that at once gives life to the young, but at the same time poses one of the greatest threats to the mother. Understanding how the tissue develops and functions is of pressing importance in determining how its control mechanisms break down in breast cancer. Here we argue that the interactions between mammary epithelial cells and their extracellular matrix (ECM) are crucial in the development and function of the tissue. Current strategies for treating breast cancer take advantage of our knowledge of the endocrine regulation of breast development, and the emerging role of stromal-epithelial interactions (Fig. 1). Focusing, in addition, on the microenvironmental influences that arise from cell-matrix interactions will open new opportunities for therapeutic intervention. We suggest that ultimately a three-pronged approach targeting endocrine, growth factor, and cell-matrix interactions will provide the best chance of curing the disease.
Topics: Animals; Breast Neoplasms; Cell Differentiation; Epithelial Cells; Extracellular Matrix; Female; Humans; Mammary Glands, Human; Mammary Neoplasms, Experimental; Mice
PubMed: 20702598
DOI: 10.1101/cshperspect.a003202 -
Environmental Health Perspectives Aug 2011Perturbations in mammary gland (MG) development may increase risk for later adverse effects, including lactation impairment, gynecomastia (in males), and breast cancer.... (Review)
Review
OBJECTIVES
Perturbations in mammary gland (MG) development may increase risk for later adverse effects, including lactation impairment, gynecomastia (in males), and breast cancer. Animal studies indicate that exposure to hormonally active agents leads to this type of developmental effect and related later life susceptibilities. In this review we describe current science, public health issues, and research recommendations for evaluating MG development.
DATA SOURCES
The Mammary Gland Evaluation and Risk Assessment Workshop was convened in Oakland, California, USA, 16-17 November 2009, to integrate the expertise and perspectives of scientists, risk assessors, and public health advocates. Interviews were conducted with 18 experts, and seven laboratories conducted an MG slide evaluation exercise. Workshop participants discussed effects of gestational and early life exposures to hormonally active agents on MG development, the relationship of these developmental effects to lactation and cancer, the relative sensitivity of MG and other developmental end points, the relevance of animal models to humans, and methods for evaluating MG effects.
SYNTHESIS
Normal MG development and MG carcinogenesis demonstrate temporal, morphological, and mechanistic similarities among test animal species and humans. Diverse chemicals, including many not considered primarily estrogenic, alter MG development in rodents. Inconsistent reporting methods hinder comparison across studies, and relationships between altered development and effects on lactation or carcinogenesis are still being defined. In some studies, altered MG development is the most sensitive endocrine end point.
CONCLUSIONS
Early life environmental exposures can alter MG development, disrupt lactation, and increase susceptibility to breast cancer. Assessment of MG development should be incorporated in chemical test guidelines and risk assessment.
Topics: Animals; Breast Neoplasms; Environmental Exposure; Female; Humans; Male; Mammary Glands, Animal; Mammary Glands, Human; Risk Assessment
PubMed: 21697028
DOI: 10.1289/ehp.1002864 -
Breast Cancer Research : BCR 2010β-Catenin plays important roles in mammary development and tumorigenesis through its functions in cell adhesion, signal transduction and regulation of... (Review)
Review
β-Catenin plays important roles in mammary development and tumorigenesis through its functions in cell adhesion, signal transduction and regulation of cell-context-specific gene expression. Studies in mice have highlighted the critical role of β-catenin signaling for stem cell biology at multiple stages of mammary development. Deregulated β-catenin signaling disturbs stem and progenitor cell dynamics and induces mammary tumors in mice. Recent data showing deregulated β-catenin signaling in metaplastic and basal-type tumors suggest a similar link to reactivated developmental pathways and human breast cancer. The present review will discuss β-catenin as a central transducer of numerous signaling pathways and its role in mammary development and breast cancer.
Topics: Animals; Breast Neoplasms; Cell Adhesion; Female; Gene Expression; Humans; Mammary Glands, Animal; Mammary Glands, Human; Mammary Neoplasms, Animal; Mice; Mice, Transgenic; Signal Transduction; Stem Cells; Wnt Proteins; beta Catenin
PubMed: 21067528
DOI: 10.1186/bcr2723 -
Journal of Mammary Gland Biology and... Sep 2010Post-natal mammary gland development requires complex interactions between the epithelial cells and various cell types within the stroma. Recent studies have illustrated... (Review)
Review
Post-natal mammary gland development requires complex interactions between the epithelial cells and various cell types within the stroma. Recent studies have illustrated the importance of immune cells and their mediators during the various stages of mammary gland development. However, the mechanisms by which these immune cells functionally contribute to mammary gland development are only beginning to be understood. This review provides an overview of the localization of immune cells within the mammary gland during the various stages of post-natal mammary gland development. Furthermore, recent studies are summarized that illustrate the mechanisms by which these cells are recruited to the mammary gland and their functional roles in mammary gland development.
Topics: Animals; Cytokines; Female; Humans; Leukocytes; Macrophages; Mammary Glands, Animal; Mammary Glands, Human; Mast Cells
PubMed: 20730636
DOI: 10.1007/s10911-010-9188-7 -
Cell Aug 2014Ectodermal appendages such as feathers, hair, mammary glands, salivary glands, and sweat glands form branches, allowing much-increased surface for functional...
Ectodermal appendages such as feathers, hair, mammary glands, salivary glands, and sweat glands form branches, allowing much-increased surface for functional differentiation and secretion. Here, the principles of branching morphogenesis are exemplified by the mammary gland and feathers.
Topics: Animals; Birds; Feathers; Female; Humans; Male; Mammals; Mammary Glands, Animal; Mammary Glands, Human; Morphogenesis; Signal Transduction
PubMed: 25171418
DOI: 10.1016/j.cell.2014.08.019 -
Journal of Mammary Gland Biology and... Jun 2013The first mouse mutation associated with a heritable defect in embryonic mammary gland development was Extratoes. It represents a functional null-mutation of the gene... (Review)
Review
The first mouse mutation associated with a heritable defect in embryonic mammary gland development was Extratoes. It represents a functional null-mutation of the gene encoding Gli3, which is best known as a transcription factor mediating canonical Hedgehog (Hh) signaling. Here we review the roles of Hh and Gli proteins in murine embryonic mammary development. We propose that an off-state for Hh signaling, mediated by Gli3-repressor, is determinant for induction of a mammary instead of hair follicle fate in the trunk surface ectoderm.
Topics: Animals; Female; Gene Expression Regulation, Developmental; Hedgehog Proteins; Humans; Mammary Glands, Animal; Mammary Glands, Human; Oncogene Proteins; Signal Transduction; Trans-Activators; Zinc Finger Protein GLI1
PubMed: 23677624
DOI: 10.1007/s10911-013-9291-7 -
Breast Cancer Research : BCR Nov 2016Lineage tracing is increasingly being utilised to probe different cell types that exist within the mammary gland. Whilst this technique is powerful for tracking cells in...
Lineage tracing is increasingly being utilised to probe different cell types that exist within the mammary gland. Whilst this technique is powerful for tracking cells in vivo and dissecting the roles of different cellular subsets in development, homeostasis and oncogenesis, there are important caveats associated with lineage tracing strategies. Here we highlight key parameters of particular relevance for the mammary gland. These include tissue preparation for whole-mount imaging, whereby the inclusion of enzymatic digestion can drastically alter tissue architecture and cell morphology, and therefore should be avoided. Other factors include the scoring of clones in three dimensions versus two dimensions, the timing of induction, and the marked variability in labelling efficiency that is evident not only between different mouse models harbouring a similar gene promoter but also within a given strain and even within a single mammary gland. Thus, it becomes crucial to visualise extensive areas of ductal tissue and to consider the intricacies of the methodology for lineage tracing studies on normal mammary development and on potential 'cells of origin' of cancer.
Topics: Animals; Biomarkers; Cell Lineage; Cell Tracking; Clonal Evolution; Female; Humans; Imaging, Three-Dimensional; Mammary Glands, Animal; Mammary Glands, Human; Molecular Imaging
PubMed: 27887631
DOI: 10.1186/s13058-016-0774-5 -
Journal of Mammary Gland Biology and... Mar 2014Milk nutrients are secreted by epithelial cells in the alveoli of the mammary gland by several complex and highly coordinated systems. Many of these nutrients are... (Review)
Review
Milk nutrients are secreted by epithelial cells in the alveoli of the mammary gland by several complex and highly coordinated systems. Many of these nutrients are transported from the blood to the milk via transcellular pathways that involve the concerted activity of transport proteins on the apical and basolateral membranes of mammary epithelial cells. In this review, we focus on transport mechanisms that contribute to the secretion of calcium, trace minerals and water soluble vitamins into milk with particular focus on the role of transporters of the SLC series as well as calcium transport proteins (ion channels and pumps). Numerous members of the SLC family are involved in the regulation of essential nutrients in the milk, such as the divalent metal transporter-1 (SLC11A2), ferroportin-1 (SLC40A1) and the copper transporter CTR1 (SLC31A1). A deeper understanding of the physiology and pathophysiology of these transporters will be of great value for drug discovery and treatment of breast diseases.
Topics: Animals; Biological Transport; Calcium; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Minerals; Trace Elements; Vitamins
PubMed: 24567109
DOI: 10.1007/s10911-014-9317-9 -
Journal of Mammary Gland Biology and... Sep 2021Mammary gland development primarily occurs postnatally, and this unique process is complex and regulated by systemic hormones and local growth factors. The mammary gland... (Review)
Review
Mammary gland development primarily occurs postnatally, and this unique process is complex and regulated by systemic hormones and local growth factors. The mammary gland is also a highly dynamic organ that undergoes profound changes at puberty and during the reproductive cycle. These changes are driven by mammary stem cells (MaSCs). Breast cancer is one of the most common causes of cancer-related death in women. Cancer stem cells (CSCs) play prominent roles in tumor initiation, drug resistance, tumor recurrence, and metastasis. The highly conserved Notch signaling pathway functions as a key regulator of the niche mediating mammary organogenesis and breast neoplasia. In this review, we discuss mechanisms by which Notch contributes to breast carcinoma pathology and suggest potentials for therapeutic targeting of Notch in breast cancer. In summary, we provide a comprehensive overview of Notch functions in regulating MaSCs, mammary development, and breast cancer.
Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinogenesis; Female; Humans; Mammary Glands, Human; Receptors, Notch; Signal Transduction; Stem Cells
PubMed: 34374886
DOI: 10.1007/s10911-021-09496-1