Download or read book Identification of Tumor Suppressor Genes in Breast Cancer by Insertional Mutagenesis and Functional Inactivation 96 Breast written by and published by . This book was released on 1998 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The development and progression of cancer result from multiple genetic changes accumulated in the cells. The identification of tumor suppressor genes inactivated and proto-oncogenes activated in mammary epithelial cells is essential to understand the genetic basis of breast cancer and is a prerequisite for development of strategies for prevention, diagnosis, and treatment. In breast cancer, loss of heterozygosity (LOR) was detected frequently on chromosome 17 and other chromosomes, suggesting unrecognized tumor suppressor genes. We are applying the novel retroviral-tagging strategy to identify the genes using chromosome 1 7-suppressed (independent of p53 and ERCAl) breast cancer cell lines. In contrast to the parental tumorigenic cell line CAL51, the suppressed sublines CAL/17-1, CAL/17-3 and CAL/17-5 display insulin-dependent growth in flasks, no growth in soft-agar culture and athymic nude mice. In this annual report, we present our results on selection for the anchorage-independent cell sublines induced by retroviral transduction of the chromosome 17-mediated suppressed cell lines CAL/ 17, in addition to successful selection for insulin-independent cell sublines. We are now in the process to conduct tumorigenicity tests in athymic nude mice and to clone genomic sequences flanking the integrated retroviral vectors.
Download or read book Identification of Tumor Suppressor Genes in Breast Cancer by International Mutagenesis and Functional Inactivation written by and published by . This book was released on 2000 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is the most common malignancy in Western women, affecting up to one in 10 women during their lifetime and approximately 40,000 women dying from the disease each year in the U.S. Tumor genetic profiling through such methods as loss of heterozygosity (LOM) screening, comparative genomic hybridization (CGll), and cDNA microarrays all point to the same conclusion that a number of genetic changes are responsible for the malignant phenotype. For example, genes involved in breast cancer progression include amplification of oncogenes such as MYC, ERBB2, CCNDl and mutation of tumor suppressor genes TP53 and CHDlL. In case of hereditary breast cancer, germline mutations of tumor suppressor genes PTEN on chromosome 10q23.3, ATM on chromosome 1 lq22-q23, BRCAl on chromosome l7q21, and BRCA2 on chromosome l3ql2.3 were also shown to involve in the tumor progression 2. These data represent a significant advance in our understanding of molecular genetics of breast cancer. However, breast cancer is a heterogeneous disease that entails complex genetic alterations in which tumor suppressor genes, oncogenes, and modulator genes were mutated. Multi step genetic alterations transform normal mammary epithelial cells via the steps of hypeiplasia, premalignant change, in situ carcinoma, invasion, and metastases. Genome-wide searching for the alterations and the elucidation of molecular events involved in these steps is the main focus for new strategies targeted at diagnosis, prevention and treatment.
Download or read book Tumor Suppressor Genes written by Wafik S. El-Deiry and published by Springer Science & Business Media. This book was released on 2008-02-03 with total page 502 pages. Available in PDF, EPUB and Kindle. Book excerpt: It has become clear that tumors arise from excessive cell proliferation and a c- responding reduction in cell death. Tumors result from the successive accumulation of mutations in key regulatory target genes over time. During the 1980s, a number of oncogenes were characterized, whereas from the 1990s to the present, the emphasis shifted to tumor suppressor genes (TSGs). It has become clear that oncogenes and tumor suppressor genes function in the same pathways, providing positive and ne- tive growth regulatory activities. The signaling pathways controlled by these genes involve virtually every process in cell biology, including nuclear events, cell cycle, cell death, cytoskeletal, cell membrane, angiogenesis, and cell adhesion effects. Tumor suppressor genes are mutated in hereditary cancer syndromes, as well as somatically in nonhereditary cancers. In their normal state, TSGs control cancer development and p- gression, as well as contribute to the sensitivity of cancers to a variety of therapeutics. Understanding the classes of TSGs, the biochemical pathways they function in, and how they are regulated provides an essential lesson in cancer biology. We cannot hope to advance our current knowledge and to develop new and more effective therapies without understanding the relevant pathways and how they influence the present approaches to therapy. Moreover, it is important to be able to access the powerful tools now available to discover these genes, as well as their links to cell biology and growth control.
Download or read book Tumor Suppressor Genes written by Wafik S. El-Deiry and published by Springer Science & Business Media. This book was released on 2008-02-03 with total page 657 pages. Available in PDF, EPUB and Kindle. Book excerpt: It has become clear that tumors result from excessive cell proliferation and a corresponding reduction in cell death caused by the successive accumulation of mutations in key regulatory target genes over time. During the 1980s, a number of oncogenes were characterized, whereas from the 1990s to the present, the emp- sis has shifted to tumor suppressor genes (TSGs). It has become clear that oncogenes and TSGs function in the same pathways, providing positive and negative growth regulatory activities. The signaling pathways controlled by these genes involve virtually every process in cell biology, including nuclear events, cell cycle, cell death, cytoskeletal, cell membrane, angiogenesis, and cell adhesion effects. Mu- tions in tumor suppressor genes have been identified in familial cancer syndromes, and the same genes in many cases have been found to be mutationally inactivated in sporadically occurring cancers. In their normal state, TSGs control cancer development and progression, as well as contribute to the sensitivity of cancers to a variety of therapeutics. Understanding the classes of TSGs, the biochemical pa- ways they function in, and how they are regulated provides an essential lesson in cancer biology. We cannot hope to advance our current knowledge and to develop new and more effective therapies without understanding the relevant pathways and how they influence the present approaches to therapy. Moreover, it is important to be able to access not only the powerful tools now available to discover these genes, but also their links to cell biology and growth control.
Download or read book Identification and Cloning a Novel Tumor Suppressor Gene in Breast Cancer written by and published by . This book was released on 1998 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: On the basis of an extensive body of cytogenetic literature as well as molecular evidence from our laboratory, we hypothesize that a tumor suppressor gene is located on the long arm of Human Chromosome 7 at the q3 1.1 band. Furthermore, we propose that inactivation of this tumor suppressor gene plays a role in the development of breast cancer. The long term objectives of the study are to identify and clone the tumor suppressor gene and to determine its function. The objectives for the requested funding period are to provide functional evidence for the existence of this tumor suppressor gene in breast cancer using microcell fusion and to clone the DNA fragment containing the putative tumor suppressor gene using a novel approach based on the introduction of Yeast Artificial Chromosomes (YACs) into breast cancer cells. This novel approach will facilitate the cloning of putative tumor suppressor genes closing the technical gaps that exist between the identification of deleted regions of genome containing putative tumor suppressor genes and the actual cloning of DNA fragments containing the candidate genes.
Download or read book Insertional Mutagenesis Strategies in Cancer Genetics written by Adam J. Dupuy and published by Springer Science & Business Media. This book was released on 2010-11-18 with total page 205 pages. Available in PDF, EPUB and Kindle. Book excerpt: The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.
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 Advances in Cancer Research written by George F. Vande Woude and published by Gulf Professional Publishing. This book was released on 2003-03-18 with total page 208 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Advances in Cancer Research series provides invaluable information on the exciting and fast-moving field of cancer research. This volume presents outstanding and original reviews on a variety of topics, including HAMLET and tumor cells; survivin and apoptosis control; retroviral insertional mutagenesis; aberrant ubiquitin-mediated proteolysis of cell cycle regulatory proteins and oncogenesis; and epigenetic variability and the evolution of human cancer. Provides invaluable information on the exciting and fast-moving field of cancer research Presents outstanding and original reviews on a variety of topics, including HAMLET and tumor cells; survivin and apoptosis control; retroviral insertional mutagenesis; aberrant ubiquitin-mediated proteolysis of cell cycle regulatory proteins and oncogenesis; and epigenetic variability and the evolution of human cancer
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 Insertional Mutagenesis as a Tool for Identifying and Characterizing Novel Candidate Cancer Genes written by Jacquelyn Jinan Roth and published by . This book was released on 2011 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer results from dynamic changes in a set of cellular genes. Mutations in oncogenes and tumor suppressor genes are responsible for converting a normal cell into a malignant one. Much research has been done to identify a large number of oncogenes and tumor suppressor genes that are frequently mutated in human cancers. These efforts suggest that the cancer genome is composed of a few commonly mutated genes along with hundreds of infrequently mutated genes. Deciphering which of the mutations are important in tumorigenesis will aid in understanding the biology of cancer as well as provide potential new therapeutic targets. Mouse models of human cancer have been used to determine the significance genetic alterations identified in human cancers. One tool that has been used for this purpose in the mouse is insertional mutagenesis. In our study, we designed a Sleeping Beauty transposon-based forward genetic screen in mice to identify candidate genes for breast cancer in the presence and absence of Cav1 mutations. Analysis of transposon integrations in all mammary tumors identified 210 common insertion sites (CISs) and candidate (CAN) genes were assigned to many of the CISs. Multiple CAN genes have been previously implicated in human breast cancers. Identifying the roles of these 210 CAN genes in tumorigenesis will determine their significance in human breast cancer. In this study, we also investigated the role of a transcription factor, Meis1, which was originally identified in murine leukemias caused by retroviral-induced insertional mutagenesis. Overexpression of Meis1 in conjunction with HoxA9 is detected in a variety of myeloid leukemia cell lines and primary human samples of acute myeloid leukemia (AML). In an effort to identify additional downstream targets of Meis1, we generated FDC-P1 cells overexpressing Meis1 in the presence or absence of HoxA9. Microarray analysis was performed on RNA isolated from these cells. A combination of bioinformatics and statistical analyses were used to look for genes with differential regulation in the presence or absence of Meis1 and HoxA9. These data were used to generate a genetic signature characteristic of Meis1 expression and shed light onto other pathways that may involve Meis1 and HoxA9.
Download or read book Tumor Suppressor Genes in Human Cancer written by David E. Fisher and published by Springer Science & Business Media. This book was released on 2000-10-26 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: David Fisher, MD, PhD, and an authoritative panel of academic, cutting-edge researchers review and summarize the current state of the field. Describing the broad roles of tumor suppressors from a perspective based in molecular biology and genetics, the authors detail the major suppressors and the pathways they regulate, including cell cycle progression, stress responses, apoptosis, and responses to DNA damage. Leading-edge and forward-looking, Tumor Suppressor Genes in Human Cancer illuminates what is currently known of tumor suppressor genes and their regulation, work that is already beginning to revolutionize cancer target elucidation, drug discovery, and treatment design.
Download or read book Identification of Novel Tumor Suppressor Genes in Breast Cancer Using Gene Tapping Technique written by Leia M. Smith and published by . This book was released on 2001 with total page 20 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is a multi-step process resulting from a number of genetic changes in cells. The role of tumor suppressor genes in breast carcinogenesis, especially at the early stage, remains largely unknown. We hypothesize that during the transformation of a breast epithelial cell, loss of function of several yet unidentified genes (tumor suppressors) results in either a partially or fully transformed phenotype. The aim of this study is to identify% novel tumor suppressor genes involved in breast epithelial transformation using the gene-trapping technique. We used the polyA-trap retroviral vector pRET for infection into non-tumorigenic human mammary epithelial cells MCF 1 0A. We screened for clones where functional genes have been "trapped" by selection for G4 18-resistance. We essentially established a gene-trapped library of MCF 1 0A clones where expression of a single gene per clone is disrupted. We screened for transformed clones using the soft-agar cloning assay for anchorage independent growth. We isolated 25 transformed clones and identified the trapped genes in 5 clones by rapid amplification of cDNA ends (3 RACE). We identified 2 known genes and 2 novel genes as putative tumor suppressor genes. Further characterization of these genes will elucidate their role in the early transformation process in breast epithelial cells.
Download or read book Genomic Approaches for Detection and Treatment of Breast Cancer written by and published by . This book was released on 2005 with total page 26 pages. Available in PDF, EPUB and Kindle. Book excerpt: The evolution of human cells into malignant derivatives is driven by the aberrant function of genes that positively and negatively regulate various aspects of the cancer phenotype, including altered responses to mitogenic and cytostatic signals, resistance to programmed cell death, immortalization, neoangiogenesis, and invasion and metastasis (Hanahan and Weinberg, 2000). The integrity of these gene functions is compromised by substantial genetic and epigenetic alterations observed in most cancer cell genomes. To understand the tumorigenic process, it is imperative to identify and characterize the genes that provide tumor cells with the capabilities requisite for their initiation and progression. However, the identities of those genes that contribute to the tumor phenotype are often concealed by the frequent alterations in genes that play no role in tumorigenesis. Identifying genes that restrain tumorigenesis (tumor suppressors) has proven especially challenging due to their recessive nature. Further complicating their discovery are the multifaceted mechanisms by which tumor suppressor genes are inactivated including changes in copy number and structure, point mutations, and epigenetic alterations (Balmain et al., 2003). Moreover, the mechanisms by which tumor suppressor genes are inhibited may vary between tumors. With this in mind, a variety of molecular and cytogenetic technologies have been used to establish extensive catalogs of genetic alterations within human cancers (Albertson et al., 2003; Futreal et al., 2004). And while it is generally accepted that highly recurrent aberrations signify changes that are important for tumor development, the causal perturbations underlying tumor genesis are often confounded by the extensive size of alterations and the large number that are incidental to the tumor phenotypes. As such, new strategies to delineate genes with functional relevance to tumor initiation and development are essential to understanding.
Download or read book Public Documents Federal Provincial Territorial Conference of Ministers of Health Toronto Ontario September 10 11 1996 written by and published by . This book was released on 1996 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Using Genetics and Genomics for the Detection and Treatment of Breast Cancer written by and published by . This book was released on 2009 with total page 20 pages. Available in PDF, EPUB and Kindle. Book excerpt: The evolution of human cells into malignant derivatives is driven by the aberrant function of genes that positively and negatively regulate various aspects of the cancer phenotype, including altered responses to mitogenic and cytostatic signals, resistance to programmed cell death, immortalization, neoangiogenesis, and invasion and metastasis(1). The integrity of these gene functions is compromised by substantial genetic and epigenetic alterations observed in most cancer cell genomes. To understand the tumorigenic process, it is imperative to identify and characterize the genes that provide tumor cells with the capabilities requisite for their initiation and progression. However, the identities of those genes that contribute to the tumor phenotype are often concealed by the frequent alterations in genes that play no role in tumorigenesis. Identifying genes that restrain tumorigenesis (tumor suppressors) has proven especially challenging due to their recessive nature. Further complicating their discovery are the multifaceted mechanisms by which tumor suppressor genes are inactivated including changes in copy number and structure, point mutations, and epigenetic alterations(2). Moreover, the mechanisms by which tumor suppressor genes are inhibited may vary between tumors. With this in mind, a variety of molecular and cytogenetic technologies have been used to establish extensive catalogs of genetic alterations within human cancers(3,4). And while it is generally accepted that highly recurrent aberrations signify changes that are important for tumor development, the causal perturbations underlying tumor genesis are often confounded by the extensive size of alterations and the large number that are incidental to the tumor phenotypes. As such, new strategies to delineate genes with functional relevance to tumor initiation and development are essential to understanding these processes.
Download or read book Tumor Suppressor Genes written by Mehmet Gunduz and published by Nova Science Publishers. This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is a devastating disease lacking an exact treatment. Recent advances in genetics and biotechnology have provided a deeper understanding of cancer biology, out of which aberrations in oncogenes and tumour suppresser genes have arisen as important etiological factors. Inactivation of tumour suppresser genes is one of the initial cellular changes that ultimately lead to tumour development. Thus, increasing knowledge about these genes aids in the development of novel therapeutic applications as well as identification of more effective and rapid molecular markers for early diagnosis and prognostic evaluation. This book provides up-to-date information on the structure, function and roles of the main tumour suppresser genes thus far identified. An important addition to the current literature in the field, this book is intended to help instructors for teaching purposes and researchers in the field of cancer biology as an overview of current knowledge.
Download or read book Tumor Suppressor Genes written by Wafik S. El-Deiry and published by Humana. This book was released on 2013-10-09 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: It has become clear that tumors result from excessive cell proliferation and a corresponding reduction in cell death caused by the successive accumulation of mutations in key regulatory target genes over time. During the 1980s, a number of oncogenes were characterized, whereas from the 1990s to the present, the emp- sis has shifted to tumor suppressor genes (TSGs). It has become clear that oncogenes and TSGs function in the same pathways, providing positive and negative growth regulatory activities. The signaling pathways controlled by these genes involve virtually every process in cell biology, including nuclear events, cell cycle, cell death, cytoskeletal, cell membrane, angiogenesis, and cell adhesion effects. Mu- tions in tumor suppressor genes have been identified in familial cancer syndromes, and the same genes in many cases have been found to be mutationally inactivated in sporadically occurring cancers. In their normal state, TSGs control cancer development and progression, as well as contribute to the sensitivity of cancers to a variety of therapeutics. Understanding the classes of TSGs, the biochemical pa- ways they function in, and how they are regulated provides an essential lesson in cancer biology. We cannot hope to advance our current knowledge and to develop new and more effective therapies without understanding the relevant pathways and how they influence the present approaches to therapy. Moreover, it is important to be able to access not only the powerful tools now available to discover these genes, but also their links to cell biology and growth control.
