Regulation of TGF-Beta Signal Transduction Pathways in Breast Cancer PDF Download

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ISBN:
Category :
Languages : en
Pages : 180

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Book Description
The goal of my studies under the BCRP fellowship is to understand the role of the Smad proteinS and the TGF-beta signal transduction pathways in breast cancer cell proliferation, tumor progression, and prognosis. In the past nine months, I have focused on identifying intracellular molecules and transcription factors that might be involved in the TGF-beta signal transduction pathway. Using both genetic and biochemical approaches, I have successfully isolated a few key molecules that are either mediator of the TGF-beta induced transcriptional response or suppressors of the TGF-beta signal pathways. Future studies will be focused on understanding the detail mechanism of how the molecules interplay in mediating TGF-beta signaling and the significance of these interactions in tumor cell proliferation, progression, and prognosis.

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Languages : en
Pages : 69

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My research goal under BCRP fellowship was to address the fundamental mechanism of TGF-beta signaling both in normal cell and cancer cells and its possible relevance to breast cancer development. Seven papers have been published or submitted during the grant period including three first-author publications. I have been involved in characterizing key signaling components (Smad3 and TFE3) and studied their function in normal TGF-beta signaling in epithelial cells. Using various experimental approaches, I discovered two distinct mechanisms by which TGF-beta signaling is altered in cancer cells. Firs, I discovered a novel mechanism by which ski oncoprotein abrogates TGF-beta signaling. Second, I found activation of Ras oncogene could disrupt TGF-beta signaling by sequestration of tumor suppressor p27 in the cytoplasm preventing its association with cdk2/cyclin E complexes. Finally, I have developed very powerful expression cloning strategies for isolating novel intracellular signal transduction proteins that mediate the pathway(s) by which TGF-beta regulates cell growth and gene expression.

Author: David A. Frank
Publisher: Springer Science & Business Media
ISBN: 1402073402
Category : Medical
Languages : en
Pages : 358

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Book Description
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."

Author: Nariyoshi Shinomiya
Publisher: Springer
ISBN: 9811072965
Category : Medical
Languages : en
Pages : 220

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Book Description
This volume focuses on the relationship between the regulation of signal transduction and disease mechanisms, and discusses how the dysregulation of intracellular signals cause diseases, cell death, carcinogenesis, and other disorders. Growth, survival, transformation, and metabolic activities at the cellular level are regulated by various intracellular signal transduction pathways. Sources that stimulate intracellular signals include intracellular stresses and signal regulators/modulators, as well as extracellular growth factors. Recent studies on signal transduction analysis using animal and human cell lines have revealed how the intracellular signals are regulated and why their dysregulation leads to pathological states such as tumorigenesis, metabolic diseases, cell death, and so on. This book highlights several important key molecules and intracellular signaling pathways such as microRNA, the TGF-beta signaling pathway, the Wnt signaling pathway and MET signaling pathway as topical and highly relevant issues in human cell research related to signal transduction. In addition to assessing the pathogenic role of these signaling pathways, it focuses on the molecular design of small molecule regulators/inhibitors of said pathways, one of the most important approaches in this area. This book offers a valuable guide, helping not only research scientists but also clinicians to understand how the dysregulation of intracellular signals leads to diseases.

Author: Daniela Malek
Publisher:
ISBN:
Category :
Languages : en
Pages : 18

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Author: B. Groner
Publisher: Springer Science & Business Media
ISBN: 3540312099
Category : Medical
Languages : en
Pages : 192

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This book does nothing less than lay out the state of development of tomorrow’s cancer drugs, directed against growth factors, growth factor receptors and intracellular signaling molecules with kinase activities. The sequencing of the human genome and insights into signaling pathways have contributed to the understanding of cancer etiology and the development of new, improved cancer drugs such as Herceptin and Glivec. The deregulation of pathways due to mutated cancer genes provides the conceptual basis for future progress. Will it be possible to derive more efficient cancer drugs?

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Languages : en
Pages : 0

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The principal goal of this project is to understand the transforming growth factor-Beta (TGF Beta) receptor signal transduction pathways and the molecular mechanism underlying the regulation of the activity of the TOFQ receptor kinases. TGF Beta could suppress the growth of breast cancer cells both in vivo and in vitro (1, 2, 3), and this function requires the expression of functional TGF Beta receptors (2, 3) and downstream signaling molecules (4). The TGF Beta family of cytokines has a wide range of biological functions including tumor suppression, extracellular matrix production, embryonic development, and regulation of differentiation(5). These functions are mediated by three specific surface receptors, Types I, II and III, all of which have been cloned (6, 7, 8, 9). The types I and II receptors for TGF Beta, T BetaRI and T BetaRll, are members of the first known receptor serine/threonine kinase family, and share 40% homology between their kinase domains. T BetaRll contains an extracellular domain which binds TGF beta, a transmembrane domain and a cytoplasmic domain with serine/threonine kinase activity. T BetaRI also has an extracellular domain even though it does not bind TGF Beta when expressed without T BetaRII. The cytoplasmic portion of T BetaRI contains a kinase domain and a membrane proximal region which contains a Oly-Ser rich sequence (OS box) that has been proposed to be important for the activation of T BetaRI (10). Both receptors exist normally as homodimers on the cell surface (11, 12) and their kinase activities are essential for signal transduction (6, 8, 9, 13). Binding of TGF Beta1 to T BetaRII induces the formation of a heteromeric complex of T BetaRI and T BetaRll (6, 8, 9, 13), which results in transphosphorylation of T BetaRI by the constitutively active TJ3Rll.

Author:
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Category :
Languages : en
Pages : 0

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The overall goal of this research project is to explore the roles of TGF-beta and components of its signaling pathways in the initiation, progression and metastasis of breast adenocarcinomas through an investigation of the disregulation of TGF-beta signal transduction. Last year, we identified and isolated three cDNAs encoding members of the Smad family and studied the TGF-beta induced phosphorylation of these molecules in a normal mammary epithelial cell line. Subsequently, we have focused on the functional role of Smad3 and Smad4 as tumor suppressors in mediating the TGF-beta signal in transactivating downstream target genes. We have also continued our investigation on the mechanism by which TGF-beta activates the expression of cyclin-dependent kinase inhibitor p15 gene in MCF7 cells as well as the importance of a paracrine loop mediated by the interactions between mammary epithelial and fibroblst cells. Results from further analysis in these directions will not only significantly contribute to an understanding of the molecular events leading to breast carcinogenesis, but also aid in the development of new therapeutics for breast cancer.

Author: Aristidis Moustakas
Publisher: Springer Science & Business Media
ISBN: 4431544097
Category : Science
Languages : en
Pages : 463

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Book Description
Transforming growth factor-β (TGF-β) is a secreted polypeptide with multifunctional properties manifested during embryonic development, adult organ physiology, and pathobiology of major diseases, including cancer and fibrotic and cardiovascular diseases. The signaling pathway of TGF-β now is rather well understood. Continuing revelations in the mechanisms of action of TGF-β provide specific mechanistic examples of how human cells lose their controlled function and behave wrongly during the development of diverse diseases. Equally important, however, is the current promise of exploiting the TGF-β pathway in combating human disease. This book comprehensively covers major areas of human disease where the involvement of TGF-β is firmly established. Simultaneously, the book highlights major gaps in knowledge and the future directions of research that can benefit human medical science. The core set of diseases where TGF-β action is well documented and are included in the book are cancer and cardiovascular and fibrotic disorders. The central aim of the book is to stimulate young scientists to enter the prolific TGF-β field and find new solutions to the problems remaining in this area of study. For this purpose the book provides authoritative educational chapters that furnish a good introduction to the field for young doctoral students, postdocs, and clinical fellows. The book also serves as a valuable reference for the aficionados in the field, who can find accessible and well-illustrated material for their teaching and lecturing activities, via which the importance of TGF-β biology is disseminated to the world of science and to the public.

Author: David A. Frank
Publisher: Springer Science & Business Media
ISBN: 9781402073403
Category : Medical
Languages : en
Pages : 372

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Book Description
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."