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Regulation Of Erbb Signaling In Breast Cancer Epithelial Cells By Cb1 Proto Oncogene Product
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Book Synopsis Regulation of ErbB Signaling in Breast Cancer Epithelial Cells by Cb1 Proto-Oncogene Product by :
Download or read book Regulation of ErbB Signaling in Breast Cancer Epithelial Cells by Cb1 Proto-Oncogene Product written by and published by . This book was released on 2002 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: A large body of evidence has shown that members of the epidermal growth factor (EUF) family play critical roles in the proliferation and differentiation of normal breast epithelial cells and are important for cell proliferation in breast cancer. The response to EGF is mediated by the transmembrane receptor tyrosine ErbB 1, or epidermal growth factor receptor (EGF-R). This receptor plays a key role in the induction of proliferation in mammary epithelial cells (MECs). Overexpression of EGF-R due to gene amplification or increased transcription is seen in a third or more of all breast cancers. Receptor overexpression may be causally linked to oncogenesis, and correlates with development and progression of tumors that are refractile to standard therapeutic approaches. Thus, EGF-R is a potential target for therapeutic intervention in the subset of women with worst prognosis on conventional treatment. Understanding and manipulating the biochemical mechanisms regulating signal transduction through EGF-R therefore represent important goals in breast cancer research, and are the focus of this study. We have proposed the hypothesis that the proto-oncoprotein Cbl provides ligand-specific negative regulation of EGF-R in epithelial cells. We and others have shown that Cbl effects EGF- mediated down-regulation, ubiquitination, and degradation of EOF-R. In the 8.5 months of this reporting period (following reactivation of the award at the place of the P.I.'s independent appointment), we have tested whether Cbl's recruitment to the receptor and its ability to ubiquitinate EGF-R depends on the nature of the stimulating ligand. In vivo, EGF stimulation of EGF-R leads to receptor downregulation and the termination of signaling, but TGF-alpha stimulation of EUF-R leads to receptor recycling and prolonged signaling. We have found that EGF-activated EUF-R binds to Cbl and undergoes polyubiquitination, but TGF-alpha-activated EGF-Rdoes the same.
Book Synopsis The Universal Gazetteer, Or a Description of the Several Empires ... in the Known World ... to which is Prefixed a Copious Introduction to Geography ... - 3. Ed by :
Download or read book The Universal Gazetteer, Or a Description of the Several Empires ... in the Known World ... to which is Prefixed a Copious Introduction to Geography ... - 3. Ed written by and published by . This book was released on 1771 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis A Novel Pathway to Down-Regulate ErbB Signaling in Mammary Epithelial Cells by :
Download or read book A Novel Pathway to Down-Regulate ErbB Signaling in Mammary Epithelial Cells written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Activation of tyrosine kinases plays a key role in cell proliferation, and ErbB receptor tyrosine kinases are specifically implicated in breast cancer. Biochemical studies have recently identified the proto-oncogene product Cbl as a negative regulator of EGF receptor and ErbB2. The Cbl-dependent negative regulation of ErbB receptors was associated with their ubiquitin modification and down-regulation from the cell surface. Based on these observations, this proposal is investigating the role of Cbl-mediated ubiquitination as a signal for targeting activated ErbB receptors to lysosomes where they undergo degradation. The work reported here has demonstrated that ubiquitin modification of EGFR is essential for its down-regulation. Furthermore, this modification is shown to be essential for EGFR trafficking between early and late endosome, while being dispensable for initial endocytosis. Further studies aim to establish the relative role of Cbl-dependent ubiqiuitinylation versus other endocytic motifs in ErbB receptor internalization, and dissect out components of the biochemical machinery that mediates ubiquitin-dependent lysosomal sorting of ErbB receptors. Elucidation of this novel pathway of ErbB receptor downregulation is likely to reveal novel targets to develop rational therapeutic agents for breast cancers with aberrant expression and/or activity of ErbB receptors.
Book Synopsis A Novel Pathway to Down-Regulate ErbB Signaling in Mammary Epithelial by :
Download or read book A Novel Pathway to Down-Regulate ErbB Signaling in Mammary Epithelial written by and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Activation of tyrosine kinases plays a key role in cell proliferation, and ErbB receptor tyrosine kinases are specifically implicated in breast cancer. Biochemical studies have recently identified the proto-oncogene product Cbl as a negative regulator of EGF receptor and ErbB2. The Cbl-dependent negative regulation of ErbB receptors was associated with their ubiquitin modification and downregulation from the cell surface. Based on these observations, this proposal is investigating the role of Cbl-mediated ubiquitination as a signal for targeting activated ErbB receptors to lysosomes where they undergo degradation. The work reported here has focused on characterization of a series of mutant forms of Cbl that are unable to mediate ubiquitination of EGFR. The analyses of these mutants support the role of ubiquitination in Cbl-mediated cell surface regulation of EGFR. Further studies will establish the intracellular targeting of downregulated ErbB receptors to lysosomes, and utilize a number of biological systems to directly explore if ubiquitination is an essential mechanism for sorting ErbB receptors to lysosomes. The present studies, thus, aim to define novel strategies to downregulate proliferative signals in breast cancer cells.
Book Synopsis Compartmentalized Signaling and Breast Cancer Cell Proliferation by :
Download or read book Compartmentalized Signaling and Breast Cancer Cell Proliferation written by and published by . This book was released on 2003 with total page 15 pages. Available in PDF, EPUB and Kindle. Book excerpt: This proposal will test a unique hypothesis that Src-family kinases direct the ErbB receptor traffic into an intracellular compartment where proliferation signals are generated. This hypothesis is based on observations that while Cb1 proto-oncoprotein facilitates the down-regulation of ErbB receptors from cell surface and functions as a negative regulator, Src tyrosine kinase enhances paradoxically enhance both the internalization of EGFR and the EGFR-mediated mitogenic signals. The proposed studies will test this hypothesis using mammary epithelial cells made to overexpress EGFR or ErbB2 together with Src. The insights gained from this model system will be directly relevant to a large proportion of breast cancers where ErbB receptors and Src-family kinases are co-overexpressed. Validation of our hypothesis will represent a shift in the current paradigm of normal and aberrant ErbB receptor signaling and may provide novel targets for therapeutic intervention relevant to ErbB-overexpressing breast cancers, which carry a significantly worse prognosis and are frequently hormone-unresponsive.
Book Synopsis Regulatory Mechanisms in Breast Cancer by : Marc E. Lippman
Download or read book Regulatory Mechanisms in Breast Cancer written by Marc E. Lippman and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 455 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Breast Cancer: Cellular and Molecular Biology [Kluwer Academic Pub lishers, 1988], we tried to present an introduction to the emerging basic studies on steroid receptors, oncogenes, and growth factors in the regulation of normal and malignant mammary epithelium. The response to this volume was superb, indicating a tremendous interest in basic growth regulatory mechanisms governing breast cancer and controlling its malignant progres sion. In the two years since its publication, much new and exciting in formation has been published and the full interplay of regulatory mechanisms is now beginning to emerge. We have divided this book into four sections that we hope will unify important concepts and help to crystallize areas of consensus and/or disagreement among a diverse group of basic and clinical scientists working on the disease. The first section is devoted to studies on oncogenes, antioncogenes, proliferation, and tumor prognosis. The first chapter, by Sunderland and McGuire, introduces the characteristics of breast cancer as studied by patho logists to establish prognostic outcome. Of particular interest is a new proto oncogene called HER-2 (or neu), which is rapidly becoming accepted as a valuable new tumor marker of poor prognosis. The second chapter, by Lee Bookstein and Lee, introduces the best known antioncogene, the retinoblas toma antioncogene, whose expression is sometimes lost in breast cancer. Malignant progression appears to be influenced by the balance of proto oncogene and antioncogene expression.
Book Synopsis Signaling the ErbB Receptors in Breast Cancer: Regulation by Compartmentalization of Heterodimetric Receptor Complexes by :
Download or read book Signaling the ErbB Receptors in Breast Cancer: Regulation by Compartmentalization of Heterodimetric Receptor Complexes written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: MEKK1 and MEKK4 play a role in the signal transduction pathways of breast cancer cell proliferation, survival, and apoptosis. Treatment with cancer chemotherapeutics, cell stresses, or anoikis activates MEKK1, which stimulates caspase activity. Caspases cleave MEKK1, and this cleavage product of MEKK1 causes apoptosis. I show that expression of the oncogene Akt blocks MEKK1-induced death by 90%. MEKK1-induced caspase activity is strongly inhibited by the expression of Akt to levels below basal. Caspases inhibition by Akt protects cells from cleavage of endogenous MEKK1 to its active form.
Book Synopsis Signaling by ErbB Receptors in Breast Cancer: Regulation by Compartmentalization of Heterodimetric Receptor Complexes by :
Download or read book Signaling by ErbB Receptors in Breast Cancer: Regulation by Compartmentalization of Heterodimetric Receptor Complexes written by and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Herein we investigated the mechanisms of MLKK1 and Stat3 signaling pathways. MEKK1 is important in apoptosis of cancer cells following detachment of cells from their matrix and following genotoxin treatment. We determined the mode by which MEKK1 causes apoptosis, and the ability of specific anti-apoptotic pathways to circumvent MEKK1-induced apoptosis. Specifically, MEKK1-induced apoptosis requires cleavage by caspase 3 and activation of the TRAIL death receptor pathway. MEKK1-induced death is potentiated by inhibition of PI-3 kinase, and is blocked by Akt through inhibition of MEKK1 cleavage. We also examined the mode of Stat3 transport through the cytoplasm to the nucleus, which has remained elusive. Stat3 is an oncogene implicated in cancer cell survival. We report that the mechanism whereby Stat3 is transported through the cytoplasm involves receptor-mediated endocytosis. Disruption of endocytosis with specific inhibitors blocks Stat3 nuclear translocation and Stat3-dependent gene regulation. Inhibition of endocytosis also blocks IL-6 and v-Src induced Stat3 activation. Therefore, receptor-mediated endocytosis may be a general mechanism for transport of cytoplasmic signaling proteins to the nucleus.
Book Synopsis Signaling Pathways and Molecular Mediators in Metastasis by : Alessandro Fatatis
Download or read book Signaling Pathways and Molecular Mediators in Metastasis written by Alessandro Fatatis and published by Springer Science & Business Media. This book was released on 2012-01-03 with total page 373 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work presents the most advanced discoveries from translational research laboratories directly involved in identifying molecules and signalling pathways that play an instrumental role in metastasis. In contrast to other works, conventionally focused on a single type of tumour, the various chapters in this book provide a broad perspective of the similarities and discrepancies among the dissemination of several solid malignancies. Through recurrent and overlapping references to molecular mechanisms and mediators, the readers will gain knowledge of the common ground in metastasis from a single source. Finally, an introductory chapter provides a clinical perspective of the problems presented by metastatic tumours for diagnosis and treatment. The work presented here is directed to researchers in tumour biology with a developing interest in metastatic dissemination as well as medical and graduate students seeking to expand and integrate the notions acquired in basic cancer biology and oncology courses.
Book Synopsis Intracellular Signaling Mediators in the Circulatory and Ventilatory Systems by : Marc Thiriet
Download or read book Intracellular Signaling Mediators in the Circulatory and Ventilatory Systems written by Marc Thiriet and published by Springer Science & Business Media. This book was released on 2012-09-26 with total page 1073 pages. Available in PDF, EPUB and Kindle. Book excerpt: The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to and remove carbon dioxide from the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to phenomenological models of nano- and microscopic events in a corrector scheme of regulated mechanisms when the vessel lumen caliber varies markedly. Therefore, investigation of flows of blood and air in physiological conduits requires an understanding of the biology, chemistry, and physics of these systems together with the mathematical tools to describe their functioning. Volume 4 is devoted to major sets of intracellular mediators that transmit signals upon stimulation of cell-surface receptors. Activation of signaling effectors triggers the release of substances stored in cellular organelles and/or gene transcription and protein synthesis. Complex stages of cell signaling can be studied using proper mathematical models, once the role of each component is carefully handled. Volume 4 also reviews various categories of cytosolic and/or nuclear mediators and illustrates some major signal transduction pathways, such as NFkappaB axis, oxygen sensing, and mechanotransduction.
Book Synopsis Concepts and Principles of Pharmacology by : James E. Barrett
Download or read book Concepts and Principles of Pharmacology written by James E. Barrett and published by Springer Nature. This book was released on 2019-12-24 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: Celebrating 100 years of HEP, this volume will discuss key pharmacological discoveries and concepts of the past 100 years. These discoveries have dramatically changed the medical treatment paradigms of many diseases and these concepts have and will continue to shape discovery of new medicinies. Newly evolving technologies will similarly be discussed as they will shape the future of the pharmacology and, accordingly, medical therapy.
Book Synopsis Neuroanatomy of Neuroendocrine Systems by : Valery Grinevich
Download or read book Neuroanatomy of Neuroendocrine Systems written by Valery Grinevich and published by Springer. This book was released on 2023-02-07 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book, experts in the field provide comprehensive descriptions of the neuroanatomy of the hypothalamic neuroendocrine systems. The book begins with an extensive discussion on the structural components of the neuroendocrine systems. The reader will be introduced to the anatomy and biology of the hypothalamus and the pituitary. The human hypothalamus is presented in particular detail using state-of-the-art imaging techniques. In the next section, the neuroanatomy of traditional hypothalamo-hypophyseal systems is highlighted, with chapters describing magnocellular neuroendocrine cells and discussing the respective types of hypothalamic neurons that regulate various pituitary hormones. Following this detailed structural and anatomical description of the neuroendocrine system, the book’s final section focuses on the hypothalamic control of neuroendocrine functions. This includes the control of circadian rhythm, metabolism and appetite via specific peptidergic circuits. This book provides essential information on the neuroanatomy and control of neuroendocrine systems, addresses cutting-edge research questions posed by recent advances in the development of potent neuroanatomical tools, and highlights the latest technologies used in neuroendocrinology research, making it a valuable reference guide for students, trainees and established researchers alike. This is the twelfth volume in the International Neuroendocrine Federation (INF) Masterclass in Neuroendocrinology series, which aims to illustrate the highest standards and to encourage the use of the latest technologies in basic and clinical research and hopes to provide inspiration for further exploration into the exciting field of neuroendocrinology. Chapter 12 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com
Book Synopsis Colon Cancer Diagnosis and Therapy by : Ganji Purnachandra Nagaraju
Download or read book Colon Cancer Diagnosis and Therapy written by Ganji Purnachandra Nagaraju and published by Springer Nature. This book was released on 2021-06-10 with total page 374 pages. Available in PDF, EPUB and Kindle. Book excerpt: Colorectal cancer (CRC) is a major global health challenge as the third leading cause for cancer related mortalities worldwide. Despite advances in therapeutic strategies, the five-year survival rate for CRC patients has remained the same over time due to the fact that patients are often diagnosed in advanced metastatic stages. Drug resistance is another common reason for poor prognosis. Researchers are now developing advanced therapeutic strategies such as immunotherapy, targeted therapy, and combination nanotechnology for drug delivery. In addition, the identification of new biomarkers will potentiate early stage diagnosis. This book is the first of three volumes on recent developments in colorectal diagnosis and therapy. Each volume can be read on its own, or together. Each volume focuses on different novel therapeutic advances, biomarkers, and identifies therapeutic targets for treatment. Written by leading international experts in the field, coverage also addresses the role of diet habits and lifestyle in reducing gastrointestinal disorders and incidence of CRC. Chapters discuss current and future diagnostic and therapeutic options for colorectal cancer patients, focusing on immunotherapeutic, nanomedicine, biomarkers, and dietary factors for the effective management of colon cancer.
Download or read book Chemical Abstracts written by and published by . This book was released on 2002 with total page 2692 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The EGF Receptor Family by : Graham Carpenter
Download or read book The EGF Receptor Family written by Graham Carpenter and published by Elsevier. This book was released on 2004-02-06 with total page 175 pages. Available in PDF, EPUB and Kindle. Book excerpt: The enormity of the literature on growth factors, plus the breadth of the biological disciplines and technical expertise required prohibits a comprehensive review by even a multi-disciplinary panel of authors. To provide an alternative that is feasible for authors and digestible by readers, this review compendium consists of a collection of articles, each covering an aspect of teh ErbB/EGF field. This compilation features articles on growth factor ligands, neuregulins, and individual receptors. The second part of the book concentrates on the biological context of the ErbB receptors, particularly in mammary development and in cancer. It concludes with a discussion of the genetic systems that have enabled significant advances in research in this area.
Book Synopsis Bone Pathology by : Jasvir S. Khurana
Download or read book Bone Pathology written by Jasvir S. Khurana and published by Springer Science & Business Media. This book was released on 2009-12-02 with total page 419 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bone Pathology is the second edition of the book, A Compendium of Skeletal Pathology that published 10 years ago. Similar to the prior edition, this book complements standard pathology texts and blends new but relatively established information on the molecular biology of the bone. Serving as a bench-side companion to the surgical pathologist, this new edition reflects new advances in our understanding of the molecular biology of bone. New chapters on soft-tissue sarcomas and soft-tissue tumors have been added as well as several additional chapters such as Soft-tissue pathology and Biomechanics. The volume is written by experts who are established in the field of musculoskeletal diseases. Bone Pathology is a combined effort from authors of different specialties including surgeons, pathologists, radiologists and basic scientists all of whom have in common an interest in bone diseases. It will be of great value to surgical pathology residents as well as practicing pathologists, skeletal radiologists, orthopedic surgeons and medical students.
Author :Fabrizio d'Adda di Fagagna Publisher :Springer Science & Business Media ISBN 13 :0387691162 Total Pages :274 pages Book Rating :4.3/5 (876 download)
Book Synopsis Advances in Molecular Oncology by : Fabrizio d'Adda di Fagagna
Download or read book Advances in Molecular Oncology written by Fabrizio d'Adda di Fagagna and published by Springer Science & Business Media. This book was released on 2007-07-18 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proceedings of the 2nd Annual IFOM-IEO Meeting on Cancer. This is a new meeting, it has about 200 attendees from Australia, Austria, Belgium, Brazil, Canada, England, France, Germany, Greece, Ireland, Italy, Japan, Netherlands, Spain, Sweden, Switzerland, and the USA. The 2nd IFOM-IEO international meeting on cancer will provide a forum in which the world’s leading cancer researchers and young scientists will discuss the latest advances in molecular oncology. The impact of recent breakthroughs in basic research and of emerging technologies on molecular medicine in cancer will be highlighted.
