scholarly journals Mammary Development and Breast Cancer: a Notch Perspective

2021 ◽  
Author(s):  
Weizhen Chen ◽  
Wei Wei ◽  
Liya Yu ◽  
Zi Ye ◽  
Fujing Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mammary Gland ◽  
Notch Signaling Pathway ◽  
Mammary Development ◽  
Comprehensive Overview ◽  
Breast Neoplasia ◽  
Common Causes ◽  
Mammary Stem ◽  
Gland Development

AbstractMammary 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.

Mammary stem cells: the root of breast cancer?

2004 ◽  
Vol 7 (9) ◽  
Author(s):  
H. A. Coppock ◽  
R. B. Clarke
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mammary Gland ◽  
Cancer Prevention ◽  
Breast Cancer Prevention ◽  
Differentiated Cells ◽  
Mammary Stem ◽  
Tissue Specific Stem Cells ◽  
Prevention And Therapy

Tissue-specific stem cells play a key role in organ homoeostasis. They are relatively well characterized in systems which undergo constant proliferation and production of differentiated cells, including the haemopoietic system, skin and intestine. However, little is known about the role and regulation of stem cells in the mammary gland. This review briefly summarizes the current understanding of the role of breast-specific stem cells in normal and cancerous tissues, and how this may identify new targets for breast cancer prevention and therapy.

scholarly journals Plasticity and Potency of Mammary Stem Cell Subsets During Mammary Gland Development

2019 ◽  
Vol 20 (9) ◽  
pp. 2357 ◽  
Author(s):  
Eunmi Lee ◽  
Raziye Piranlioglu ◽  
Max S. Wicha ◽  
Hasan Korkaya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Mammary Epithelial ◽  
Stem Cell Markers ◽  
Quiescent State ◽  
Mammary Stem Cells ◽  
Mammary Stem ◽  
Gland Development

It is now widely believed that mammary epithelial cell plasticity, an important physiological process during the stages of mammary gland development, is exploited by the malignant cells for their successful disease progression. Normal mammary epithelial cells are heterogeneous and organized in hierarchical fashion, in which the mammary stem cells (MaSC) lie at the apex with regenerative capacity as well as plasticity. Despite the fact that the majority of studies supported the existence of multipotent MaSCs giving rise to both basal and luminal lineages, others proposed lineage restricted unipotent MaSCs. Consistent with the notion, the latest research has suggested that although normal MaSC subsets mainly stay in a quiescent state, they differ in their reconstituting ability, spatial localization, and molecular and epigenetic signatures in response to physiological stimuli within the respective microenvironment during the stages of mammary gland development. In this review, we will focus on current research on the biology of normal mammary stem cells with an emphasis on properties of cellular plasticity, self-renewal and quiescence, as well as the role of the microenvironment in regulating these processes. This will include a discussion of normal breast stem cell heterogeneity, stem cell markers, and lineage tracing studies.

scholarly journals AP-2γ is Required for Maintenance of Pluripotent Mammary Stem Cells

2020 ◽  
Author(s):  
Vivian W. Gu ◽  
Edward Cho ◽  
Dakota T. Thompson ◽  
Victoria C. Cassady ◽  
Nicholas Borcherding ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mammary Gland ◽  
Target Genes ◽  
Mammary Development ◽  
Conditional Knockout ◽  
List Type ◽  
Mammary Stem Cells ◽  
Regenerative Capacity ◽  
Mammary Stem ◽  
Deficient Mice

SUMMARYMammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (MaSCs) into basal and luminal lineages. The AP-2γ transcription factor, encoded by Tfap2c, has a central role in mammary gland development but its effect in mammary lineages and specifically MaSCs is largely unknown. Herein, we utilized an inducible, conditional knockout of Tfap2c to elucidate the role of AP-2γ in maintenance and differentiation of MaSCs. Loss of AP-2γ in the basal epithelium profoundly altered the transcriptomes and decreased the number of cells within several clusters of mammary epithelial cells, including adult MaSCs and luminal progenitors.AP-2γ regulated the expression of genes known to be required for mammary development including C/EBPβ, IκBα, and Rspo1. As a result, AP-2γ-deficient mice exhibited repressed mammary gland ductal outgrowth and inhibition of regenerative capacity. The findings demonstrate that AP-2γ is required for maintenance of pluripotent MaSCs and their ability to develop mammary gland structures.HighlightsAP-2γ-deficient mice exhibited repressed ductal outgrowth and regenerative capacityLoss of AP-2γ reduced the number of mammary stem and luminal progenitor cellsAP-2γ target genes, including C/EBPβ, IκBα, and Rspo1, regulate mammary developmentAP-2γ is required for maintenance of pluripotent mammary stem cellseTOC blurbGu, Cho and colleagues utilized a conditional knockout of Tfap2c to examine transcriptional effects of AP-2γ on mammary stem cells. Single cell analysis demonstrated that AP-2γ-deficient mice have decreased numbers of mammary stem cells and alteration of genes required for mammary development including C/EBPβ, IκBα, and Rspo1. They demonstrate that AP-2γ is necessary for maintenance of pluripotent mammary stem cells.

scholarly journals Mammary development in the embryo and adult: new insights into the journey of morphogenesis and commitment

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev169862
Author(s):  
Christine J. Watson ◽  
Walid T. Khaled
Keyword(s):  
Mammary Gland ◽  
Progenitor Cell ◽  
Mammary Gland Development ◽  
Mammary Development ◽  
Three Dimensions ◽  
Lineage Specification ◽  
Technological Advances ◽  
Mammary Stem ◽  
Psychosocial Benefits ◽  
Gland Development

ABSTRACTThe mammary gland is a unique tissue and the defining feature of the class Mammalia. It is a late-evolving epidermal appendage that has the primary function of providing nutrition for the young, although recent studies have highlighted additional benefits of milk including the provision of passive immunity and a microbiome and, in humans, the psychosocial benefits of breastfeeding. In this Review, we outline the various stages of mammary gland development in the mouse, with a particular focus on lineage specification and the new insights that have been gained by the application of recent technological advances in imaging in both real-time and three-dimensions, and in single cell RNA sequencing. These studies have revealed the complexity of subpopulations of cells that contribute to the mammary stem and progenitor cell hierarchy and we suggest a new terminology to distinguish these cells.

scholarly journals Insight into mammary gland development and tumor prevention in a newly developed metastatic mouse model of breast cancer

2021 ◽  
Author(s):  
Briana To ◽  
Carson Broeker ◽  
Jing-Ru Jhan ◽  
Rachel Rempel ◽  
Jonathan P Rennhack ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mouse Model ◽  
Cyclin D1 ◽  
Mammary Gland Development ◽  
Mammary Tumors ◽  
Mammary Development ◽  
Conditional Knockout ◽  
Altered Regulation ◽  
Gland Development

The development of breast cancer has been observed due to altered regulation of mammary gland developmental processes. Thus, a better understand of the normal mammary gland development can reveal possible mechanism in how normal cells are re-programmed to become malignant cells. E2F1-4 are part of the E2F transcription factor family with varied roles in mammary development. However, little is known about the role of E2F5 in mammary gland development. A combination of scRNAseq and predictive signature tools demonstrate the presence of E2F5 in the mammary gland and showed altered activity during the various phases of mammary gland development and function. Testing the hypothesis that E2F5 regulates mammary function, we generated a mammary-specific E2F5 knockout mouse model, resulting in modest mammary gland development changes. However, after a prolonged latency the E2F5 conditional knockout mice developed highly metastatic mammary tumors with metastases in both the lung and liver. Transplantation of the tumors revealed metastases to lymph nodes that was enriched through serial transplantation. Through whole genome sequencing and RNAseq analysis we identified, and then confirmed in vivo, that Cyclin D1 was dysregulated in E2F5 conditional knockout mammary glands and tumors. Based on these findings, we propose that loss of E2F5 leads altered regulation of Cyclin D1, which facilitates the development of mammary tumors.

scholarly journals Notch3 marks clonogenic mammary luminal progenitor cells in vivo

2013 ◽  
Vol 203 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Daniel Lafkas ◽  
Veronica Rodilla ◽  
Mathilde Huyghe ◽  
Larissa Mourao ◽  
Hippokratis Kiaris ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Progenitor Cells ◽  
Mammary Gland Development ◽  
Notch Signaling Pathway ◽  
Luminal Progenitor ◽  
Mammary Stem ◽  
Luminal Progenitor Cells ◽  
Elevated Expression ◽  
Gland Development

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2SAT transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

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