Is the Regenerative Capacity of the Mammary Gland Contained With Those Mammary Cells That Express the Progesterone Receptor? Implications for Breast Cancer PDF Download
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Languages : en
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Recent transgenic studies have demonstrated that targeted overexpression of the A and B isoforms of the progesterone receptor (PR) to the mammary gland results in excessive ductal branching and alveolar growth respectively. Based on the above, we hypothesized that mammary-specific stem cells are present as a subgroup within those epithelial cells that express PR. To determine whether a stem cell population is contained within the PR expressing cell population (PR(+)), a PR-lacZ knockin mouse in combination with fluorescent-activated cell sorting (FACS) was utilized to separate PR(+) from PR( - ) mammary cells; both cell populations would then be evaluated for their regenerative capacity by transplantation into the cleared mammary fat pad of a host animal. FACS analysis applied to the PR-lacZ mammary gland provided a significantly enriched (70%) PR(+) mammary epithelial cell population that maintained lacZ expression in culture. Although, PR(+) and PR( - ) enriched mammary epithelial cell populations were transplanted into mammary fat pads, these host animals were lost to Tropical Storm 'Allison'; estimation of the regenerative potential of the above mammary epithelial cell populations will have to await the expansion of the PR-lacZ colony.
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Languages : en
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Recent transgenic studies have demonstrated that targeted overexpression of the A and B isoforms of the progesterone receptor (PR) to the mammary gland results in excessive ductal branching and alveolar growth respectively. Based on the above, we hypothesized that mammary-specific stem cells are present as a subgroup within those epithelial cells that express PR. To determine whether a stem cell population is contained within the PR expressing cell population (PR(+)), a PR-lacZ knockin mouse in combination with fluorescent-activated cell sorting (FACS) was utilized to separate PR(+) from PR( - ) mammary cells; both cell populations would then be evaluated for their regenerative capacity by transplantation into the cleared mammary fat pad of a host animal. FACS analysis applied to the PR-lacZ mammary gland provided a significantly enriched (70%) PR(+) mammary epithelial cell population that maintained lacZ expression in culture. Although, PR(+) and PR( - ) enriched mammary epithelial cell populations were transplanted into mammary fat pads, these host animals were lost to Tropical Storm 'Allison'; estimation of the regenerative potential of the above mammary epithelial cell populations will have to await the expansion of the PR-lacZ colony.
Author: C. Wayne Bardin
Publisher: Raven Press (ID)
ISBN:
Category : Medical
Languages : en
Pages : 488
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Languages : en
Pages : 48
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Both the growth and the development of the mammary gland are controlled by the female hormones estrogen, prolactin and progesterone, and by interactions between the epithelial and stromal compartments of the breast. Changes in the regulation of any of these processes may lead to breast cancer. We have investigated the role of progesterone in the process of sidebranching and alveologenesis in the mammary gland using mice lacking the progesterone receptor which are defective in these processes. By reconstituting murine mammary glands in vivo, we have shown that the progesterone receptor is required only in epithelial cells for proper sidebranching and alveologenesis to occur. Our studies indicate that progesterone acts in a paracrine manner and suggest that Wnt-4 is a mediator of the paracrine signals released from progesterone receptor-positive cells. In addition, we have characterized the role of the estrogen receptor (ER) in regulating the proliferation of breast cancer cells. We postulate that the ability of ER to control cyclin Dl expression and proliferation of breast cancer cells may be acquired during breast cancer progression. This is indicated by the fact that ectopic expression of the estrogen receptor in human epithelial cells does not, on its own, enable signaling between the ER and the cyclin D1 gene. Moreover, others have demonstrated that the ER-positive cells in the mammary epithelium are distinguishable from those that are actively mitotic. Finally, our work indicates that the effects of deletion of the prolactin receptor (PrlR) from mammary epithelial cells closely phenocopy the consequences of deleting cyclin Dl from these cells. We suggest that activation of the PrlR by its ligand results in the production of insulin-like growth factor-2 which in turn induces cyclin D1 synthesis in these cells.
Author: Maria del Mar Vivanco
Publisher: Humana
ISBN: 9781493925186
Category : Science
Languages : en
Pages : 0
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The identification of normal and breast cancer stem cells has offered a new vision of this heterogeneous disease and new hopes for its prognosis and treatment. This volume provides an overview of recent developments in mammary stem cell research and discusses the many varieties of approaches used by researchers to investigate the properties and functions of mammary stem cells. The beginning chapters provide readers with an introduction to mammary stem cells, and the processes used to characterize stem cells and isolate them via fluorescent activated cell sorting. The next few chapters discuss DNA and mRNA sequencing, proteomic techniques to help profile cells, lentiviral cell transduction for gene expression, and in vivo lineage tracing. The final few chapters are dedicated to following stem cells from their initial niche to the new microenvironment at their metastasis site, and to studying these cells using physical and mathematical approaches. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Authoritative and cutting-edge, Mammary Stem Cells: Methods and Protocols aims to help members of the scientific community explore the behavior of stem cells and how to work with them in order to guide the design of new and complimentary strategies to be applied in the clinic with the ultimate end goal of fighting breast cancer.
Author: Orla M. Conneely
Publisher: Springer Science & Business Media
ISBN: 3540734937
Category : Science
Languages : en
Pages : 211
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Book Description
Progestins play a key role in reproductive endocrinology and as pharmaceutical drugs for contraception and in combined hormone therapy. To further our understanding of progestin action in the mammary gland, an international symposium, attended by leading researchers from academia and industry, was held in Berlin, 21–23 March 2007. Genetic mouse models helped to elucidate the role of progestins, both in normal breast development and in disease. Mechanistic molecular studies inspired the design of new progestins with improved tissue selectivity. In addition, the clinical impact of progesterone receptor agonists and antagonists for the prevention and treatment of breast cancer was discussed.
Author: Mark Douglas Aupperlee
Publisher:
ISBN:
Category : Breast
Languages : en
Pages : 396
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Author: Leon P. Bignold
Publisher: Springer Science & Business Media
ISBN: 9783764371562
Category : Medical
Languages : en
Pages : 396
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Book Description
Tumors can be induced by a variety of physical and chemical carcinogens. The resulting tumor cells are usually abnormal in their morphology and behavior and transmit their abnormalities to their daughter tumor cells. Most theories of the pathogenesis of tumors suggest that carcinogens in some way cause alterations either of the genomes or of inheritable patterns of gene expression in normal cells, which then cause morphological and behavioral changes. This volume presents a collection of articles aimed at the question by what genetic or epigenetic mechanisms carcinogens can cause morphological abnormalities of tumor cells. It includes reviews of cellular targets of known carcinogens, and presents varying viewpoints of how morphological abnormalities and the actions of carcinogens might be related. The volume will be of interest to all those who are involved in cancer research or in the prevention, diagnosis or management of tumors in humans or animals.
Author: Mohit Kumar Jolly
Publisher: MDPI
ISBN: 3039367242
Category : Medical
Languages : en
Pages : 512
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Book Description
Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.
Author: Klaus Ebnet
Publisher: Springer
ISBN: 3319144669
Category : Science
Languages : en
Pages : 228
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This work provides a state-of-the art overview on the most relevant aspects of cell polarity. Volume 2 discusses the physiological and pathophysiological relevance of cell polarity. It especially focuses on pathophysiological conditions in which one or several aspects of cell polarity are impaired, and in which a loss of cell polarity possibly contributes to disease (e.g. epithelial-to-mesenchymal transition in cancer, role of polarity proteins in cancer). Both volumes are intended for professors, group leaders and researchers in cell biology as well as for medical professionals working in anatomy, cell biology, physiology, pathology and tumor biology.
Author: Maria Lorella Gianni
Publisher: MDPI
ISBN: 3039289233
Category : Science
Languages : en
Pages : 368
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Book Description
Human milk is uniquely tailored to meet infants’ specific nutritional requirements. However, it is more than just “milk”. This dynamic and bioactive fluid allows mother–infant signalling over lactation, guiding the infant in the developmental and physiological processes. It exerts protection and life-long biological effects, playing a crucial role in promoting healthy growth and optimal cognitive development. The latest scientific advances have provided insight into different components of human milk and their dynamic changes over time. However, the complexity of human milk composition and the synergistic mechanisms responsible for its beneficial health effects have not yet been unravelled. Filling this knowledge gap will shed light on the biology of the developing infant and will contribute to the optimization of infant feeding, particularly that of the most vulnerable infants. Greater understanding of human milk will also help in elucidating the best strategies for its storage and handling. The increasing knowledge on human milk’s bioactive compounds together with the rapidly-advancing technological achievements will greatly enhance their use as prophylactic or therapeutic agents. The current Special Issue aims to welcome original works and literature reviews further exploring the complexity of human milk composition, the mechanisms underlying the beneficial effects associated with breastfeeding, and the factors and determinants involved in lactation, including its promotion and support.
