Rb and Tumorigenesis examines how recent advances have demonstrated the interaction of Rb with chromatin remodeling enzymes. This new title explores the potential roles of these interactions in Rb functions and provides some evidence that distinct Rb co-repressor may target different genes in different phases of the cell cycle. This book will interest cell biologists, graduate students and researchers.

This volume covers the mechanisms of pRb inactivation detailing repressive mechanisms commonly associated to cancer, and representative of the experimentally relevant tests used in the establishment of cancer diagnosis and prognosis. Chapters contain protocols and in-depth discussions for commonly used experimental approaches to assess the status and function of components of the pRb pathway, including pRb itself, in cell lines and biological samples.Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, The Retinoblastoma Protein aims to serve as a guide to assist molecular cancer biologists in their search for understanding of the molecular functions of this preeminent tumor suppressor.

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."

Cancer arises from an accumulation of multiple mutations that may occur in oncogenes, tumor suppressor genes or DNA repair genes. Tumor suppressors control cell cycle and growth and mutations or alterations in these suppressors can be associated with the uncontrolled growth of malignant tumors. In this project, tumor suppressors were studied highlighting a new protein called RlZ. The goal is to use x-ray crystallography to study the molecules. The results will be important to understanding the role of the new regulator protein RlZ in tumorigenesis in breast cancer. This IDEA project focused on the first steps in the process, i.e. production, purification and crystallization of the proteins. Notable progress was made in identifying the PR domain in RlZ that is directly linked to tumor suppression. PR is underexpressed in breast cancer. Feasibility for structural studies of this new protein motif (PR) was established.

The integrity of the RB tumor suppressor pathway is critical for inhibition of inappropriate proliferation and suppression of tumor development in a wide variety of human tissues. RB has been shown to play a number of distinct roles in contributing to tumor suppression; studies have implicated the RB pathway in DNA damage response, genome instability, establishment of senescence, and promotion of differentiation, among other processes. Despite intensive research, however, the specific functions of RB as they relate to individual disease contexts and distinct facets of cellular stress response remain unclear. Herein, research is directed at first unmasking the immediate underlying impact of RB deletion in vivo , and then subsequently probing the specific disease-relevant functions of RB deficiency during DNA damage response and subsequent liver tumorigenesis. Tissue specific deletion of RB revealed a profound induction of E2F-mediated DNA replication that was characterized by hyper-physiological formation of pre-replication complexes. These phenotypes were not accompanied by productive mitoses. Uniquely, RB-deficient hepatocytes accumulated aberrant ploidy and significant levels of DNA damage. Furthermore, in vitro and in vivo analyses demonstrate the LXCXE-binding function of RB, while dispensable for E2F-promoter association, is required for mediating appropriate transcriptional control during DNA damage response in the liver. Such aberrant responses were mediated preferentially through E2F3. Long-term studies demonstrated that disruption of LXCXE-binding accelerated DNA damage mediated tumorigenesis in vivo and gene expression profiling revealed that the transcriptional program mediated by this function of RB was associated with progression to HCC in humans. Surprisingly, gene expression profiling also revealed an unexpected role for RB in modulation of immune response gene transcription. Together, these studies demonstrate and establish highly tissue-specific and context-depentent roles for RB in transcriptional control and tumor suppression.

The purpose of this book is to provide a contemporary overview of the causes and consequences of prostate cancer from a cellular and genetic perspective. Written by experts in the fields of epidemiology, toxicology, cell biology, genetics, genomics, cell-cell interactions, cell signaling, hormone signaling, and transcriptional regulation, the text covers aspects of prostate cancer from disease initiation to metastasis. Chapters explore in depth the cells of origin for prostate cancer, its genomic subtypes, neural transcription factors in disease progression, epigenetic regulation of chromatin, and many other topics. This book distinguishes itself from other texts on prostate cancer by its focus on cellular and genetic mechanisms, as opposed to clinical diagnosis and management. As a result, this book will be of broad interest to basic and translational scientists with familiarity of these topics, as well as to trainees at earlier stages of their research careers.