Download or read book The Role of E2f5 in Mammary Gland Development and Breast Cancer Progression written by Briana To and published by . This book was released on 2020 with total page 129 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dysregulation of mammary developmental processes have resulted in breast cancer development and progression. Thus, understanding normal mammary gland development is critical to understanding how cancer cells are initiated and maintained. Transcriptomic profiling of various mammary gland developmental phases, including virgin, pregnancy, lactation and involution, revealed distinct gene expression patterns associated at each stage. Pathway analysis predicted a role for transcription factors E2F1-4 during different stages of development. The importance of E2Fs in mammary development was confirmed by the defects observed in the mammary glands of mice deficient for various E2Fs. To examine if compensation occurs among activator E2Fs in the mammary gland, we analyzed mammary gland development in double E2F knockout mice. Our analysis revealed that compensation does occur among activator E2Fs in the mammary gland. However, this compensation appears to be very specific, as E2F2 can compensate for E2F1 but not E2F3 loss. Although the role of E2F1-4 has been characterized in mammary gland development, little is known about E2F5, an E2F demonstrating repressor activity. Using bioinformatic analysis, we predicted a role for E2F5 in terminal end bud differentiation and developmental stages. To further examine the role of E2F5 in normal mammary gland development, we generated a mammary-specific E2F5 knockout mouse model (E2F5CKO). Analysis of mammary gland development in E2F5CKO mice reveal only modest mammary gland defects. However, we found that E2F5CKO animals develop mammary tumors after a prolonged latency. Using transcriptomic profiling, we identified oncogenes that are dysregulated in E2F5CKO tumors, potentially contributing to tumorigenesis. Through these studies, we have identified a novel role of E2F5 as a tumor suppressor in breast cancer and further elucidated roles of E2Fs in mammary gland development.
Download or read book Discerning the Role of FOXA1 in Mammary Gland Development and Breast Cancer written by Gina M. Bernardo and published by . This book was released on 2011 with total page 255 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is a heterogeneous disease with distinct subtypes that are predictive of patient prognosis. Luminal subtype tumors confer the most favorable prognosis due to ERa-positivity and response to endocrine therapies. In contrast, basal-like subtype tumors confer the worst prognosis due to intrinsic resistance to chemotherapy and the lack of targeted therapies. The forkhead box transcription factor, FOXA1, is found exclusively in luminal tumors, and positively correlates with ERa and survival. Prior to our study, FOXA1 was known to mediate the development of many tissues and be required for ERa transcriptional activity in breast cancer cells. Given these findings, along with the requirement for ERa in mammary morphogenesis, we hypothesized that FOXA1 would be similarly necessary in this process. Using Foxa1 null mice, we found FOXA1 is required for hormone-induced ductal invasion. Mammary glands null for Foxa1 lack epithelial ERa. The regulation of ERa by FOXA1 is similarly observed in breast cancer cells. These results revealed that FOXA1 is not only required for ERa activity, but also for its expression, and provided a mechanism for the ductal phenotype in Foxa1 knockout glands. The positive correlation between FOXA1 and ERa in breast tumors is significant, but not perfect. FOXA1 is also expressed in luminal breast tumors and cell lines in the absence of ERa prompting us to investigate an ERa-independent role for FOXA1 in maintaining the luminal subtype. FOXA1 silencing in ERa-positive and ERa-negative luminal breast cancer cells decreases luminal gene expression, and concomitantly increases basal gene expression. These cells are also more aggressive in vitro, indicating a shift toward the basal phenotype. FOXA1 binds to a subset of basal genes, and thus, is likely orchestrating repression of these genes at the transcriptional level. These data implicate FOXA1 as a mediator of breast cellular plasticity, and suggest that therapeutically reducing FOXA1 in luminal tumors will increase disease aggressiveness. Combined, this dissertation research has detailed the role for FOXA1 in the normal mammary gland and its importance in luminal breast cancer. Our results have led to numerous testable hypotheses that will continue to advance our understanding of FOXA1 in breast cancer.
Download or read book A Novel Role for C EBP In Mammary Development and Breast Cancer written by and published by . This book was released on 1999 with total page 49 pages. Available in PDF, EPUB and Kindle. Book excerpt: The objective of this fellowship is to characterize the roles which C/EBpalpha and beta play in normal mammary gland development and breast cancer. In general, C/EBPalpha is predominantly expressed at high levels in terminally differentiated, growth arrested cells and the C/EBPALPHABeta isoforms, most notably LIP, are expressed at high levels' in actively proliferating cells. LIP can act as dominant negative isoform, which when dimerized with other C/EBP family members suppresses transcriptional activity. Consequently, an increase in LIP levels may lead to excessive cellular proliferation. Overexpression of LIP in the mammary gland of transgenic mice results in ductal hyperplasia. Additionally, overexpression of LIP in TM3 mouse mammary cells results in an increase in proliferation via an increase in the number of cells entering S- phase of the cell cycle. Similarly, transplantation of TM3 cells overexpressing LIP into the cleared mammary fat pads of mice also results in very proliferative out- growths. These observations are consistent with the hypothesis that increased LIP expression may inhibit terminal differentiation and provide a selective growth advantage facilitating tumor progression.
Download or read book Regulation of Mammary Stem Cells and Breast Cancer by the Co factor of LIM Domains Clim Transcriptional Regulator written by Michael Salmans and published by . This book was released on 2014 with total page 113 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent advancements in mammary gland biology demonstrate conflicting models in maintenance of basal and luminal cell compartments by either unipotent or bipotent mammary stem cells. However, the molecular mechanisms underlying control of the basal cell compartment, including stem cells, remain poorly understood. Here we explore the currently unknown transcriptional mechanisms of basal stem cell (BSC) maintenance, in addition to addressing the role of the basal cell compartment in preserving luminal cell fate and promoting development of human breast tumors of luminal origin. We discover a novel function for the Co-factor of LIM domains (Clim) transcriptional regulator in promoting mammary gland branching morphogenesis and breast tumorigenesis through maintenance of the basal stem cell population. The transcriptional networks coordinated by Clims in basal mammary epithelial cells also preserve the identity of luminal epithelial cells, demonstrating a crosstalk between these two cellular compartments. Furthermore, we correlate developmental gene expression data with human breast cancer to investigate the role of developmental pathways during the initiation and progression of breast cancer. The gene regulatory networks identified during development, including those specifically coordinated by Clims, correlate with breast cancer patient outcome, suggesting these genes play an important role in the progression of breast cancer. We also explore the role of Agr2 a putative protein disulfide isomerase (PDI) initially identified as an estrogen-responsive gene in breast cancer cell lines, in normal mammary gland development and breast cancer. While Agr2 expression in breast cancer is positively correlated with estrogen receptor (ER) expression, it is upregulated in both hormone dependent and independent carcinomas. Agr2 expression is developmentally regulated in the mammary gland, with maximum expression during late pregnancy and lactation. We show that [Subscript Agr2] facilitates normal lobuloalveolar development by regulating mammary epithelial cell proliferation. In conclusion, the estrogen-responsive Agr2, a candidate breast cancer oncogene, regulates epithelial cell proliferation and lobuloalveolar development in the mammary gland. The pro-proliferative effects of Agr2 may explain its actions in early tumorigenesis.
Download or read book Gene Targets of C EBP Beta Involved in Mammary Gland Development and Breast Cancer written by and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Previous analyses of C/EBP beta KO mice have demonstrated an important role for this transcription factor in early developmental events in the mammary gland. In the pre-pubescent mouse, progesterone receptor (PR) expression is uniform along the ducts, but becomes non-uniform following the completion of ductal morphogenesis. However, PR remained uniformly expressed in the C/EBP beta KO glands. Similar increases in prolactin receptor (PrIR) and estrogen receptor were also observed. When PR expression was examined in the PrIR KO gland, a uniform pattern of expression was also observed. In order to determine if these effects were epithelial cell autonomous and independent of any alterations in systemic hormone levels, PrIR KO and Stat5A/B double KO mammary glands were transplanted into the cleared fat pads of nude mice.
Download or read book The Role of E2Fs in Mammary Gland Development written by April R. Sandy and published by . This book was released on 2006 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: The mammary gland is a highly organized structure that takes cues from a variety of cellular pathways and messengers to direct its development and changes--one of those classes of messengers is the E2F family of transcription factors. While loss of all three E2Fs that direct cellular proliferation results in loss of normal development, the specific roles of these factors are largely uncharacterized, especially in the mammary gland. Examining the effects of single and combinatorial deletions of the E2F family members will present a better picture of the roles of these factors in developing the structure of glands. The myc oncogene and E2F transcription factors are known to have ties to cancer, and the development of cancer in mammary glands is directly related to abnormal development, leading to oncogenic events. Therefore, a better understanding of the effect of E2Fs on development will inevitably give rise to a more insightful view of how cancer forms in the mammary gland. Advisor: Dr. Gustavo Leone.
Download or read book Growth Factors and Metalloproteinases in Breast Cancer Development and Progression written by and published by . This book was released on 1995 with total page 10 pages. Available in PDF, EPUB and Kindle. Book excerpt: The overall goal of this project is to test the hypothesis that the action of growth factors on mammary neoplasia and tumor progression is mediated, at least in part, by their action on the genes for matrix-degrading metalloproteinases (MMPs). This hypothesis will be tested using transgenic mouse model systems of breast cancer. Initial studies involved the generation of transgenic mice expressing the MMP matrilysin under the control of the MTV promoter/enhancer. One line of transgenic mice demonstrated the induction of an alveolar phenotype in virgin female mice similar to that observed in MMTV-TGFa transgenic mice. These results provide support for the initial hypothesis that TOFa may be affecting mammary gland development by enhancing MMP gene expression, although further confirmation of the results is required. These studies will assist in determining the most effective use of synthetic inhibitors of MMPs as potential therapeutic agents for the treatment of breast cancer.
Download or read book Signal Transduction in Cancer written by David A. Frank and published by Springer Science & Business Media. This book was released on 2002-12-31 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."
Download or read book Nutritional Antioxidant Therapies Treatments and Perspectives written by Kaïs Hussain Al-Gubory and published by Springer. This book was released on 2018-03-10 with total page 572 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book offers a collection of expert reviews on the use of plant-based antioxidant therapies in disease prevention and treatment. Topics discussed include the uses of plant and nutritional antioxidants in the contexts of reproductive health and prenatal development, healthcare and aging, noncommunicable chronic diseases, and environmental pollution. The text is complemented by a wealth of color figures and summary tables.
Download or read book Cell Cycle Regulation written by Philipp Kaldis and published by Results and Problems in Cell Differentiation. This book was released on 2006-06-26 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a state-of-the-art summary of the latest achievements in cell cycle control research with an outlook on the effect of these findings on cancer research. The chapters are written by internationally leading experts in the field. They provide an updated view on how the cell cycle is regulated in vivo, and about the involvement of cell cycle regulators in cancer.
Download or read book Telomeres and Telomerase in Cancer written by Keiko Hiyama and published by Springer Science & Business Media. This book was released on 2009-03-18 with total page 375 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, an enzyme that maintains telomeres and endows eukaryotic cells with immortality, was first discovered in tetrahymena in 1985. In 1990s, it was proven that this enzyme also plays a key role in the infinite proliferation of human cancer cells. Now telomere and telomerase are widely accepted as important factors involved in cancer biology, and as promising diagnostic tools and therapeutic targets. Recently, role of telomerase in “cancer stem cells” has become another attractive story. Until now, there are several good books on telomere and telomerase focusing on biology in ciliates, yeasts, and mouse or basic sciences in human, providing basic scientists or students with updated knowledge.
Download or read book Medicinal Plants written by Halina Maria Ekiert and published by Springer Nature. This book was released on 2021-09-01 with total page 900 pages. Available in PDF, EPUB and Kindle. Book excerpt: Medicinal plant research is an evergreen subject. There is a tremendous increase in popularity of herbal medicine in traditional medicine, ethnomedicine, modern medicine and as over the counter food supplements. Even after this increased demand, supply is neither uniform nor assured as most of these plants are collected from wild. In developing countries of tropical and subtropical regions where majority of herbal drugs are produced, this is not organised sector making it vulnerable to several malpractices, hence standardization of all aspects required. This has also negative impact on biodiversity and conservation of plants as well as supply of uniform material. This book is aimed to provide up to date information about sustainable use of selected medicinal plants, their active ingredients and efforts made to domesticate them to ensured uniform supply. Development of agrotechnology, biotechnology and cultivation practices using conventional and non-conventional methods are presented. Where these efforts will lead the medicinal plant research and future perspective are discussed. The chapters are written by well recognised group leaders in working in the field. The book contains topics on general biology of medicinal plants, their sustainable use and, cultivation and domestication efforts. A uniform chapter structure has been designed to keep consistency. The book will be useful for academicians, agriculturists, biotechnologists and researcher, and industries involved in manufacturing herbal drugs and supplementary products.
Download or read book Bioactive Molecules in Food written by Jean-Michel Mérillon and published by Springer Nature. This book was released on 2019-01-25 with total page 2353 pages. Available in PDF, EPUB and Kindle. Book excerpt: This reference work provides comprehensive information about the bioactive molecules presented in our daily food and their effect on the physical and mental state of our body. Although the concept of functional food is new, the consumption of selected food to attain a specific effect existed already in ancient civilizations, namely of China and India. Consumers are now more attentive to food quality, safety and health benefits, and the food industry is led to develop processed- and packaged-food, particularly in terms of calories, quality, nutritional value and bioactive molecules. This book covers the entire range of bioactive molecules presented in daily food, such as carbohydrates, proteins, lipids, isoflavonoids, carotenoids, vitamin C, polyphenols, bioactive molecules presented in wine, beer and cider. Concepts like French paradox, Mediterranean diet, healthy diet of eating fruits and vegetables, vegan and vegetarian diet, functional foods are described with suitable case studies. Readers will also discover a very timely compilation of methods for bioactive molecules analysis. Written by highly renowned scientists of the field, this reference work appeals to a wide readership, from graduate students, scholars, researchers in the field of botany, agriculture, pharmacy, biotechnology and food industry to those involved in manufacturing, processing and marketing of value-added food products.
Download or read book Introduction to the Cellular and Molecular Biology of Cancer written by Margaret Knowles and published by Oxford University Press. This book was released on 2005-07-28 with total page 555 pages. Available in PDF, EPUB and Kindle. Book excerpt: This title includes the following features: Great breadth of coverage inone volume: covers all aspects of cancer, in a concise and affordable format;Provides a comprehensive introduction to the initiation, development, andtreatment of cancer; Chapter are written by experts in each field, giving astate-of-the-art summary of each topic; Extensive references provide links toall the relevant literature, facilitating further study
Download or read book Pediatric Germ Cell Tumors written by A. Lindsay Frazier and published by Springer Science & Business Media. This book was released on 2013-10-28 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt: Germ cell tumors are relatively rare compared with other malignancies, and compilations of knowledge that encompass the entire spectrum of the disease are lacking. This textbook, written by the foremost authorities in the field, rectifies the situation by discussing in depth a broad range of topics, including biology, epidemiology, pathology, treatment, and late effects. Bearing in mind that germ cell tumors are most prevalent in the adolescent and young adult age group, causes of disease and treatment approaches in pediatric and adult patients are compared and contrasted. By spanning the entire life course, from prenatal origins of disease through to treatment in adults and late effects of treatment, the editors have produced a book that will be of interest to both pediatric and adult oncologists.
Download or read book Genetic Basis for Carcinogenesis written by Takamatsu no Miya Hi Gan Kenkyū Kikin. International Symposium and published by Taylor & Francis Group. This book was released on 1990 with total page 342 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume brings together the latest studies on various aspects of molecular oncology. It emphasizes the current view that oncogenes and suppressor genes need to be discussed in the same context.
Download or read book Vitamin D and Human Health written by Simon Spedding and published by MDPI. This book was released on 2019-02-21 with total page 307 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "Vitamin D and Human Health" that was published in Nutrients
