-
Acta Obstetricia Et Gynecologica... Nov 2015The aim of this article is to review the physiology of progesterone and focus on its physiological actions on tissues such as endometrium, uterus, mammary gland,... (Review)
Review
INTRODUCTION
The aim of this article is to review the physiology of progesterone and focus on its physiological actions on tissues such as endometrium, uterus, mammary gland, cardiovascular system, central nervous system and bones. In the last decades, the interest of researchers has focused on the role of progesterone in genomic and non-genomic receptor mechanisms.
MATERIALS AND METHODS
We searched PubMed up to December 2014 for publications on progesterone/steroidogenesis.
RESULTS AND CONCLUSIONS
A better understanding of the biological genomic and non-genomic receptor mechanisms could enable us in the near future to obtain a more comprehensive knowledge of the safety and efficacy of this agent during hormone replacement therapy (natural progesterone), in vitro fertilization (water-soluble subcutaneous progesterone), in traumatic brain injury, Alzheimer's disease and diabetic neuropathy, even though further clinical studies are needed to prove its usefulness.
Topics: Cell Membrane; Cell Nucleus; Central Nervous System; Embryo Implantation; Endometrium; Female; Humans; Mammary Glands, Human; Menstrual Cycle; Osteoporosis; Progesterone; Receptors, Progesterone
PubMed: 26358238
DOI: 10.1111/aogs.12771 -
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 -
Molecular Medicine (Cambridge, Mass.) Aug 2018Serum amyloid A (SAA) proteins were isolated and named over 50 years ago. They are small (104 amino acids) and have a striking relationship to the acute phase response... (Review)
Review
Serum amyloid A (SAA) proteins were isolated and named over 50 years ago. They are small (104 amino acids) and have a striking relationship to the acute phase response with serum levels rising as much as 1000-fold in 24 hours. SAA proteins are encoded in a family of closely-related genes and have been remarkably conserved throughout vertebrate evolution. Amino-terminal fragments of SAA can form highly organized, insoluble fibrils that accumulate in "secondary" amyloid disease. Despite their evolutionary preservation and dynamic synthesis pattern SAA proteins have lacked well-defined physiologic roles. However, considering an array of many, often unrelated, reports now permits a more coordinated perspective. Protein studies have elucidated basic SAA structure and fibril formation. Appreciating SAA's lipophilicity helps relate it to lipid transport and metabolism as well as atherosclerosis. SAA's function as a cytokine-like protein has become recognized in cell-cell communication as well as feedback in inflammatory, immunologic, neoplastic and protective pathways. SAA likely has a critical role in control and possibly propagation of the primordial acute phase response. Appreciating the many cellular and molecular interactions for SAA suggests possibilities for improved understanding of pathophysiology as well as treatment and disease prevention.
Topics: Acute-Phase Reaction; Animals; Atherosclerosis; Collagenases; Humans; Lipid Metabolism; Mammary Glands, Human; Maternal Health; Matrix Metalloproteinases; Neoplasms; Sarcoidosis, Pulmonary; Serum Amyloid A Protein
PubMed: 30165816
DOI: 10.1186/s10020-018-0047-0 -
Developmental Cell Jun 2022The breast is a dynamic organ whose response to physiological and pathophysiological conditions alters its disease susceptibility, yet the specific effects of these...
The breast is a dynamic organ whose response to physiological and pathophysiological conditions alters its disease susceptibility, yet the specific effects of these clinical variables on cell state remain poorly annotated. We present a unified, high-resolution breast atlas by integrating single-cell RNA-seq, mass cytometry, and cyclic immunofluorescence, encompassing a myriad of states. We define cell subtypes within the alveolar, hormone-sensing, and basal epithelial lineages, delineating associations of several subtypes with cancer risk factors, including age, parity, and BRCA2 germline mutation. Of particular interest is a subset of alveolar cells termed basal-luminal (BL) cells, which exhibit poor transcriptional lineage fidelity, accumulate with age, and carry a gene signature associated with basal-like breast cancer. We further utilize a medium-depletion approach to identify molecular factors regulating cell-subtype proportion in organoids. Together, these data are a rich resource to elucidate diverse mammary cell states.
Topics: Animals; Breast; Breast Neoplasms; Female; Humans; Mammary Glands, Animal; Pregnancy; Proteomics; Transcriptome
PubMed: 35617956
DOI: 10.1016/j.devcel.2022.05.003 -
Neoplasia (New York, N.Y.) Dec 2020The cellular heterogeneity of breast cancers still represents a major therapeutic challenge. The latest genomic studies have classified breast cancers in distinct... (Review)
Review
The cellular heterogeneity of breast cancers still represents a major therapeutic challenge. The latest genomic studies have classified breast cancers in distinct clusters to inform the therapeutic approaches and predict clinical outcomes. The mammary epithelium is composed of luminal and basal cells, and this seemingly hierarchical organization is dependent on various stem cells and progenitors populating the mammary gland. Some cancer cells are conceptually similar to the stem cells as they can self-renew and generate bulk populations of nontumorigenic cells. Two models have been proposed to explain the cell of origin of breast cancer and involve either the reprogramming of differentiated mammary cells or the dysregulation of mammary stem cells or progenitors. Both hypotheses are not exclusive and imply the accumulation of independent mutational events. Cancer stem cells have been isolated from breast tumors and implicated in the development, metastasis, and recurrence of breast cancers. Recent advances in single-cell sequencing help deciphering the clonal evolution within each breast tumor. Still, few clinical trials have been focused on these specific cancer cell populations.
Topics: Animals; Breast Neoplasms; Disease Models, Animal; Disease Susceptibility; Female; Humans; Incidence; Mammary Glands, Human; Mice; Neoplasm Staging; Neoplastic Stem Cells; Risk Assessment; Stem Cells
PubMed: 33142233
DOI: 10.1016/j.neo.2020.09.009 -
The Journal of Clinical Investigation Nov 2007Breast cancer is not a single disease, but rather is composed of distinct subtypes associated with different clinical outcomes. Understanding this heterogeneity is key... (Review)
Review
Breast cancer is not a single disease, but rather is composed of distinct subtypes associated with different clinical outcomes. Understanding this heterogeneity is key for the development of targeted cancer-preventative and -therapeutic interventions. Current models explaining inter- and intratumoral diversity are the cancer stem cell and the clonal evolution hypotheses. Although tumor initiation and progression are predominantly driven by acquired genetic alterations, recent data implicate a role for microenvironmental and epigenetic changes as well. Comprehensive unbiased studies of tumors and patient populations have significantly advanced our molecular understanding of breast cancer, but translating these findings into clinical practice remains a challenge.
Topics: Breast Neoplasms; Cell Transformation, Neoplastic; Disease Progression; Epigenesis, Genetic; Female; Humans; Mammary Glands, Human; Neoplasm Metastasis; Stem Cells
PubMed: 17975657
DOI: 10.1172/JCI33295 -
TheScientificWorldJournal 2021Breast cancer is the highest public detected cancer among female population in the majority of countries worldwide. Breast self-examination (BSE) is a useful screening...
Breast cancer is the highest public detected cancer among female population in the majority of countries worldwide. Breast self-examination (BSE) is a useful screening tool to empower women and raise awareness about their breast tissues and help detect any breast abnormalities when they occur. This study aimed to assess the level of female university students' knowledge and practice of BSE. A self-administered questionnaire was used to assess the knowledge about breast cancer and related items, and an observation checklist was used to test practicing BSE using a breast simulator. Eighty-six students participated in the study, 58.1% studying nursing and 41.9% studying clinical nutrition in the third (40.7%) or the fourth level (59.3%). Of them, 24.4% had previous family history of breast cancer. The majority of the students (80.2%) had previous information about breast cancer acquired from different sources, university studies (57%), the Internet (45%), and social media (41%). Findings showed good scores (≥70%) regarding signs and symptoms and risk factors of breast cancer; however, low knowledge scores (<70%) were detected regarding general knowledge about breast cancer disease, methods of early detection and management, and applying steps of practicing BSE. Roughly all the students (96.5%) have heard about BSE, and 69.8% knew the time to do BSE; however, only 31.4% practice it regularly. Three barriers to practice were dominant among students who do not have a breast problem (39.7%), do not know how to do it (37.9%), and being busy 31%. On the other hand, breast cancer early detection purpose and the presence of family history of breast cancer were considered facilitators to regular practice BSE. A statistically significant relationship existed between knowledge about the steps of applying the BSE and regular practicing. A training program should be implemented to increase the level of awareness about BC and practicing BSE.
Topics: Adult; Breast Neoplasms; Breast Self-Examination; Cross-Sectional Studies; Early Detection of Cancer; Female; Health Knowledge, Attitudes, Practice; Humans; Mammary Glands, Human; Middle East; Risk Factors; Students; Surveys and Questionnaires; Universities
PubMed: 34007246
DOI: 10.1155/2021/6640324 -
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 -
Gene Feb 2020TBX3, a member of the ancient and evolutionary conserved T-box transcription factor family, is a critical developmental regulator of several structures including the... (Review)
Review
TBX3, a member of the ancient and evolutionary conserved T-box transcription factor family, is a critical developmental regulator of several structures including the heart, mammary glands, limbs and lungs. Indeed, mutations in the human TBX3 lead to ulnar mammary syndrome which is characterized by several clinical malformations including hypoplasia of the mammary and apocrine glands, defects of the upper limb, areola, dental structures, heart and genitalia. In contrast, TBX3 has no known function in adult tissues but is frequently overexpressed in a wide range of epithelial and mesenchymal derived cancers. This overexpression greatly impacts several hallmarks of cancer including bypass of senescence, apoptosis and anoikis, promotion of proliferation, tumour formation, angiogenesis, invasion and metastatic capabilities as well as cancer stem cell expansion. The debilitating consequences of having too little or too much TBX3 suggest that its expression levels need to be tightly regulated. While we have a reasonable understanding of the mutations that result in low levels of functional TBX3 during development, very little is known about the factors responsible for the overexpression of TBX3 in cancer. Furthermore, given the plethora of oncogenic processes that TBX3 impacts, it must be regulating several target genes but to date only a few have been identified and characterised. Interestingly, while there is compelling evidence to support oncogenic roles for TBX3, a few studies have indicated that it may also have tumour suppressor functions in certain contexts. Together, the diverse functional elasticity of TBX3 in development and cancer is thought to involve, in part, the protein partners that it interacts with and this area of research has recently received some attention. This review provides an insight into the significance of TBX3 in development and cancer and identifies research gaps that need to be explored to shed more light on this transcription factor.
Topics: Animals; Cell Transformation, Neoplastic; Disease; Gene Expression Regulation, Developmental; Humans; T-Box Domain Proteins; Transcription Factors
PubMed: 31669645
DOI: 10.1016/j.gene.2019.144223 -
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