Download or read book RNA Binding Proteins as Novel Oncogenes and Tumor Suppressors in Breast Cancer written by and published by . This book was released on 2007 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: Post transcriptional control of gene expression is particularly important for oncoproteins and cell cycle proteins because their sustained synthesis favors cell growth rather than differentiation, a hallmark of the neoplastic phenotype. Control is exerted via the opposing actions of the RNA-binding proteins AUF1 and HuR. AUF1 triggers degradation of mRNA subsets while HuR promotes mRNA stabilization. Phase I of this work is to examine the effects of AUF1 and HuR expression levels on global gene expression in human breast carcinoma cells. Phase II is to assess roles of AUF1 and HuR in cellular proliferation and tumorigenesis in vivo. Previously, we discovered that AUF1 knockdown elevates expression of c-myc proto-oncogene by in vivo association with the mRNA, accelerates breast cancer cell proliferation, and alters their cell-cell adhesion properties. To explain the biological effects of AUF1 knockdown, we performed cDNA microarray analyses during the final funding period to identify AUF1's target mRNA subsets and their regulation by AUF1.

Download or read book RNA Binding Proteins as Novel Oncoproteins and Tumor Suppressors in Breast Cancer written by and published by . This book was released on 2006 with total page 11 pages. Available in PDF, EPUB and Kindle. Book excerpt: Posttranscriptional control of gene expression is particularly important for oncoproteins and cell cycle proteins because their sustained synthesis favors cell growth rather than differentiation, a hallmark of the neoplastic phenotype. Control is exerted via the opposing actions of the RNA-binding proteins AUF1 and HuR. AUF1 triggers degradation of mRNA subsets while HuR promotes mRNA stabilization. Phase I of this work is to examine the effects of AUF1 and HuR expression levels on global gene expression in human breast carcinoma cells. Phase II is to assess roles of AUF1 and HuR in cellular proliferation and tumorigenesis in vivo. During this funding period, we discovered that AUF1 knockdown accelerates breast cancer cell proliferation and may convert cells to a highly metastatic state. Moreover, AUF1 knockdown elevates expression of the c-myc proto-oncogene, consistent with accelerated proliferation. mRNP immunoprecipitation and RT-PCR revealed that AUF1 binds c-myc mRNA in cells. Our results reveal a new paradigm for tumor metastasis and invasion in breast cancer.

Download or read book Tumor Suppressor Genes written by Katherine R. Polinsky and published by Nova Publishers. This book was released on 2007 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: A tumour suppressor gene is a gene that reduces the probability that a cell in a multicellular organism will turn into a tumor cell. A mutation or deletion of such a gene will increase the probability of the formation of a tumor. Unlike oncogenes, tumor suppressor genes generally follow the 'two-hit hypothesis', which implies that both alleles that code for a particular gene must be affected before an effect is manifested. This is due to the fact that if only one allele for the gene is damaged, the second can still produce the correct protein. However, there are cases where mutations in only one allele will cause an effect. A notable example is the gene that codes for p53. Tumor suppressor genes, or more precisely, the proteins for which they code, either have a dampening or repressive effect on the regulation of the cell cycle or promote apoptosis, and sometimes do both. This book presents new and important research from throughout the world.

Download or read book Perturbation of RNA Binding Protein Regulation in Cancer written by Pradeep Chaluvally Raghavan and published by Frontiers Media SA. This book was released on 2021-08-25 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Holland Frei Cancer Medicine written by Robert C. Bast, Jr. and published by John Wiley & Sons. This book was released on 2017-03-10 with total page 2004 pages. Available in PDF, EPUB and Kindle. Book excerpt: Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates

Download or read book Development of Novel RNA and Protein Based Cancer Therapeutics by Either Silencing of Potential Oncogenes Or Active Restoration of a Tumor Suppressor Gene written by Inga Neef and published by . This book was released on 2009 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Viruses Genes and Cancer written by Eric Hunter and published by Springer. This book was released on 2017-08-25 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume focuses on virus-host cell interactions, cellular genes acquired or modulated by viruses, the pathological effects of these interactions, and therapeutic interventions. Several chapters specifically address the role of viruses and genes – such as oncogenes, proto-oncogenes, or tumor suppressor genes – in the etiology of human cancer. Oncogenic signaling by PI3 kinase, mTOR, Akt, or the major cancer drivers MYC and RAF, and the role of tumor suppressors like p53, are discussed in detail. The volume also explores the emerging role of noncoding RNAs such as microRNAs in tumorigenesis and cancer therapeutics, and offers new insights into the role of HIV-host interactions relevant to pathogenesis and treatment. Gathering contributions written by leading scientists in their respective fields, the volume offers a valuable resource for researchers and clinicians alike.

Download or read book Molecular Biology of Cancer written by Fiona Macdonald and published by Taylor & Francis. This book was released on 2004-06-02 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Biology of Cancer has been extensively revised and covers heredity cancer, microarray technology and increased study of childhood cancers. It continues to provide a detailed overview of the process which lead to the development and proliferation of cancer cells, including the techniques available for their study. It also describes the means by which tumor suppressor genes and oncogenes may be used in the diagnosis and in determining the prognosis of a wide variety of cancers, including breast, genitourinary, lung and gastrointestinal cancer.

Download or read book Long Non Coding RNAs in Cancer written by Alfons Navarro and published by Humana. This book was released on 2022-06-25 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume presents techniques needed for the study of long non-coding RNAs (lncRNAs) in cancer from their identification to functional characterization. Chapters guide readers through identification of lncRNA expression signatures in cancer tissue or liquid biopsies by RNAseq, single Cell RNAseq, Phospho RNAseq or Nanopore Sequencing techniques; validation of lncRNA signatures by Real time PCR, digital PCR or in situ hybridization; and functional analysis by siRNA or CRISPR based methods for lncRNA silencing or overexpression. Lipid based nanoparticles for delivery of siRNAs in vivo, lncRNA-protein interactions, viral lncRNAs and circRNAs are also treated in this volume. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and practical, Long Non-Coding RNAs in Cancer aims to provide a collection of laboratory protocols, bioinformatic pipelines, and review chapters to further research in this vital field.

Download or read book Kokusai jinkennen written by and published by . This book was released on 1968 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book written by and published by . This book was released on 2000 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book MicroRNAs in Cancer written by Cesar Lopez-Camarillo and published by CRC Press. This book was released on 2013-02-22 with total page 426 pages. Available in PDF, EPUB and Kindle. Book excerpt: MicroRNA (miRNA) biology is a cutting-edge topic in basic as well as biomedical research. This is a specialized book focusing on the current understanding of the role of miRNAs in the development, progression, invasion, and metastasis of diverse types of cancer. It also reviews their potential for applications in cancer diagnosis, prognosis, and th

Download or read book Genome Wide Nucleic Acid Protein Interactions in Breast Cancer written by and published by . This book was released on 2003 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since many types of breast cancer remain untreatable, the research proposal aims to develop novel genomic technology to identify potential therapeutic targets and to aid in diagnosing various types of breast cancer at the molecular level. The overarching goal of the proposal is to develop a technology to screen nucleic-acid protein interactions on a genome scale with a focus on understanding complexes involved in breast cancer. In order to identify the regulatory networks of interactions between RNAs and proteins, we propose to develop a rapid genome-scale method to determine the specific RNA targets and RNA binding sites of proteins. The aims were to 1) discover RNA targets of specific RNA binding proteins and protein complexes including the breast cancer susceptibility gene BRCA1, and 2) define the RNA sequences recognized by proteins using novel nanotechnologies including development of optically encoded beads containing both a unique optical signature and a specific oligonucleotide. We have completed the proof of concept experiments for the bead-based assay, identified RNAs that may interact with a BRCA1 complex and are complementing the technology with genome-wide chromatin immunoprecipitation.

Download or read book The Opposing Roles of Nucleophosmin and the ARF Tumor Suppressor in Breast Cancer written by and published by . This book was released on 2007 with total page 78 pages. Available in PDF, EPUB and Kindle. Book excerpt: The ARF tumor suppressor protein plays an important role in the tumor surveillance of human cancer. In the search for novel ARF binding proteins, we uncovered NPM. Despite the important role ARF plays in the regulation of tumorigenesis, alterations selectively affecting its ability to negate NPM function have not been studied. In our proposed study, we aimed to determine the impact of ARF-NPM interactions in the pathogenesis of breast cancer. To this end, we have found that overexpression of NPM in the absence of ARF is a powerful transforming event. NPM promotes tumorigenesis without affecting genomic stability, implying that the subsequent tumors should remain diploid, a hallmark of ARF-null breast cancers. Indeed, when we analyzed sixty breast carcinomas, NPM was highly overexpressed in 50% of cases. We have begun further analyses of how NPM promotes tumor formation and have discovered that it does so through ribosome dysregulation, opening up the door to new therapeutic targets in breast cancer: protein synthesis.

Download or read book Posttranscriptional Gene Regulation by the RNA Binding Protein HuR in Two Disease Models written by Matthew M. Gubin and published by . This book was released on 2012 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt: The RNA binding protein HuR binds to the AU-rich (ARE) regions of labile mRNAs, such as proto-oncogenes, stabilizing their mRNA and facilitating their translation into protein. HuR has been described to control genes in multiple areas of the acquired capabilities model of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established. In additional to controlling genes involved in cancer, HuR also regulates genes involved in the immune system including. We investigated the role of HuR in two disease models: triple-negative breast cancer and allergic asthma. To understand the role of HuR in both cancer and allergic asthma we generated novel overexpression and underexpression models. Unexpectedly breast cancer tumors overexpressing HuR grew significantly slower than control tumors. Tumors overexpressing HuR had fewer blood vessels implicating HuR's role in angiogenesis. The putative mechanism seems to be an anti-angiogenic effect by increasing expression of TSP1 but also surprisingly, down-regulating VEGF, a target which HuR normally increases. Additionally, we generated and used lentiviral shRNA targeting HuR, transgenic mice overexpressing HuR in CD4+ T cells and a HuR conditional knockout (KO) mouse to understand the role of HuR in Th2 polarization. We show that the Th2 master transcription factor GATA-3, as well as IL-4 and IL-13 are regulated at the level of mRNA stability by HuR. Surprisingly, Th2 polarized cells from homozygous HuR knockout mice showed increased IL-2, IL-4 and IL-13 expression at both mRNA and protein levels but no changes in GATA-3 or IFNgamma. Despite these alterations in Th2 cytokine levels, HuR conditional KO mice have similar allergic airway inflammation as control mice.

Download or read book Cloning of Tumor Suppressor Genes in Breast Cancer written by and published by . This book was released on 2003 with total page 15 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer arises through the accumulation of genetic alterations that affect two classes of genes, oncogenes and tumor suppressor genes. These genes must be identified for several reasons. Characterization of the genes that drive carcinogenesis will facilitate a better understanding of cancer development. As part of this big picture, we have studied tumor suppressor genes involved in breast cancer. A tumor suppressor candidate, DBC2 was analyzed. DBC2 is a structurally new gene and its function remains to be studied. DBC2 is composed of a BAS domain, protein-protein interacting domains, and DNA binding domain. DBC2 expression is extinguished in more than half of breast tumors we tested. Methylation analysis of tumor cells revealed hypermethylation of the CpG islands in the DBC2 promoter region. Additionally, we have discovered somatic mutations of DBC2 in breast cancer. These mutations are accompanied by LOB. When DBC2 expression was induced in tumor cells, the cell growth was hindered. In contrast naturally occurring mutants did not suppress growth of the tumor cells. Our findings suggest that DBC2 is the target of mutations at 8p22.

Download or read book Investigating the Role of RNA binding Proteins in Tumor Response to DNA Damage inducing Chemotherapy written by Molly A. Bird and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite immense progress in the biological understanding and treatment of cancer over the past several decades, cancer remains a leading cause of mortality worldwide. Even with the emergence of molecularly-targeted therapies and immunotherapy, cytotoxic agents that induce DNA damage remain first-line drugs in the clinic. Unfortunately, the majority of patients will develop resistance to DNA-damaging chemotherapy and relapse. Recent studies indicate that RNA-binding proteins (RBPs) appear to play a particularly important role in cancer, and may contribute to chemoresistance, but the field is still at an early stage and nothing has yet progressed towards translational utility. This is at least partially due to a lack of systematic discovery tools and tractable human-relevant mouse models for in vivo screening. To address these challenges, we first created a computational platform, Transite, that systematically infers RBPs influencing gene expression through changes in RNA stability. As a proof of principle, we applied Transite to RNA expression data from cancer patients with naïve or chemoresistant tumors, identified several RBP regulators of the DNA damage response, and identified hnRNPC as a new modulator of chemotherapeutic resistance. Second, to enable the identification of new RBPs that affect chemosensitivity in high-grade serous ovarian carcinoma (HGSOC) we performed a targeted CRISPRi screen in vitro against 579 RBPs to identify those that cause sensitivity or resistance to cisplatin, oxaliplatin, paclitaxel, or olaparib. The screen implicated several known and novel RBPs in affecting sensitivity to chemotherapy in HGSOC, including the RNA-modifying enzyme ADAR1, which we subsequently validated. As an initial step towards in vivo testing and validation of the CRISPRi screen, we have devised methods to improve the engraftment and aggressivene ss of an orthotopic HGSOC CRISPRi-functionalized xenograft mouse model. This involved serial in vivo transplantation studies to generate tumor and ascites-producing lines, several of which became more aggressive with subsequent passaging in mice. With further optimization, these lines can be used to enable in vivo screening of novel RBP targets that emerged from our in vitro CRISPRi screen. Taken together, the efforts described in this thesis serve as a critical resource to enable the identification of RBP-targeted combination chemotherapy treatments that could enhance therapeutic responses to anti-cancer therapy.