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 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 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 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 Breast Cancer written by Marc Lacroix and published by Nova Biomedical Books. This book was released on 2008 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is characterised by the accumulation of genetic alterations, including point mutations and loss of entire DNA regions ("loss of heterozygosity" or LOH). Among genes that are affected by such events, the "tumour suppresser genes" (TSGs) have a peculiar interest since they often occupy pivotal positions in regulatory networks that control the cell cycle and/or encompass various signal transduction cascades. While a number of genes have been suggested as candidate TSGs in breast cancer, only a few of them have been confirmed in this status. They include TP53, BRCA1, BRCA2...and are mainly involved in the control of DNA repair, cell proliferation, apoptosis and signalling. Some TSGs are linked to familial (hereditary) forms of breast cancer. The exact definition of what is a TSG is still debated. Recently, genes not affected by mutation or even LOH, but occasionally methylated have been considered as TSGs.

Download or read book Understanding Breast Cancer Genetics written by Barbara T. Zimmerman and published by Univ. Press of Mississippi. This book was released on 2004 with total page 142 pages. Available in PDF, EPUB and Kindle. Book excerpt: Health & Sickness -- Consumer Health This book by a scientist whose background is in cellular and molecular biology examines the fearsome disease that strikes one in eight women in the United States. Although women are more likely to die of heart disease or of lung cancer, a diagnosis of breast cancer is the medical pronouncement that a woman is most likely to fear. It kills more than 40,000 Americans annually. Why are some women more vulnerable than others? The interplay between genetics and environment is suspected. Thus this book for general readers will help them understand the genetic bases of both sporadic and inherited breast cancers. Although only five to ten percent of breast cancer patients have inherited mutations in these genes, all women need to understand the genetic implications of the disease. In clear, concise language Barbara T. Zimmerman guides the reader through the complexities, discussing in detail the genes that are known to increase susceptibility and the ways they are passed on. Examining the general biology of breast cancer, Zimmerman describes how sporadic and inherited forms of the disease arise and how the location of the tumors can affect the body. She discusses genetic mutations and their roles in the development of tumors and tells how these potentially cancer-inducing genes were discovered. Covered too are the issues of risk, prevention, screening, diagnosis, therapy, and genetic testing and counseling. Zimmerman concludes with a comprehensive analysis of current research and with an emphasis on how a woman's understanding of inherited breast cancer can help doctors seeking to design better methods for prevention and therapy. A useful list of resources for further information about the genetic causes of breast cancer is included. Barbara T. Zimmerman did her graduate work in experimental pathology and her post-doctoral research in the cellular and molecular processes of disease. Widely published, she is the manager of the Denver-based firm Biomedical Communication and Consulting.

Download or read book Identification of Novel Tumor Suppressor Genes for Breast Cancer written by and published by . This book was released on 2006 with total page 43 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chromosomal deletions are very common events in breast cancer. However, no TSGs have been identified from most of recurrent deletions and few identified TSGs do not account for the risk of majority of breast cancer. In additional to the classical TSGs, there are haplo-insufficient TSGs which defy the identification through mutation analysis and may be quite common. By using a new system to generate random chromosomal deletions, we identified a ~3Mbp deletion in mouse chromosome 3, which was associated with tumorigenesis. The expression of Fat4 in the deleted region was inactivated due to promoter methylation in the second allele of Fat4, and the re-expression of Fat4 suppressed the tumorigenecity, suggesting Fat4 as a strong candidate for breast tumor suppressor genes. We also found that Fat4 expression was lost in a high proportion of human breast cancers, some of which were attributed to Fat4 promoter methylation.

Download or read book Suppressor Genes in Breast Cancer written by and published by . This book was released on 1999 with total page 24 pages. Available in PDF, EPUB and Kindle. Book excerpt: Several tumor suppressor genes (TSGs) have been cloned and found to be mutated in a variety of cancers, including breast cancer. However, few breast cancer specific TSGs are known. The purposes of this proposal are to: (1) generate cDNA expression libraries from reduction mammoplasties, (2) use a novel functional assay to clone new TSGs specific to human breast cancer, and (3) identify their characteristics, regulation and function. We are utilizing the tetracycline (tet) regulable system. We have constructed a cDNA library from normal human breast epithelia and cloned this cDNA library into a vector that is negatively regulated by tat repressor (tetR) and simultaneously expresses the enhanced green fluorescent protein. These vectors were then co-transfected into LCC6, MDA231, and MCF-7 cells that have the capability to express tetR. Upon withdrawal of tet, the repressed expression of the cDNA of interest is released, and the cDNA is expressed. Using a novel dye retained in nonproliferating cells, we were able to identify growth inhibited clones which were then sorted by Flow Cytometry. This functional screen has provided the basis for identifying TSGs that are expressed in the growth inhibited cells. Using PCR, we have obtained and sequenced two insert sequences. One is a putative TSG on chromosome #9 (725 bp) but the other sequence is vector DNA.

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 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 Mammography and Beyond written by National Research Council and published by National Academies Press. This book was released on 2001-07-23 with total page 311 pages. Available in PDF, EPUB and Kindle. Book excerpt: Each year more than 180,000 new cases of breast cancer are diagnosed in women in the U.S. If cancer is detected when small and local, treatment options are less dangerous, intrusive, and costly-and more likely to lead to a cure. Yet those simple facts belie the complexity of developing and disseminating acceptable techniques for breast cancer diagnosis. Even the most exciting new technologies remain clouded with uncertainty. Mammography and Beyond provides a comprehensive and up-to-date perspective on the state of breast cancer screening and diagnosis and recommends steps for developing the most reliable breast cancer detection methods possible. This book reviews the dramatic expansion of breast cancer awareness and screening, examining the capabilities and limitations of current and emerging technologies for breast cancer detection and their effectiveness at actually reducing deaths. The committee discusses issues including national policy toward breast cancer detection, roles of public and private agencies, problems in determining the success of a technique, availability of detection methods to specific populations of women, women's experience during the detection process, cost-benefit analyses, and more. Examining current practices and specifying research and other needs, Mammography and Beyond will be an indispensable resource to policy makers, public health officials, medical practitioners, researchers, women's health advocates, and concerned women and their families.

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 Using Insertional Mutagenesis to Identify Breast Cancer Drivers and Therapy Resistance Genes in Mice written by and published by . This book was released on 2018 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Identification of Tumor Suppressor Genes by Genetic and Epigenetic Genome Scanning written by and published by . This book was released on 2008 with total page 64 pages. Available in PDF, EPUB and Kindle. Book excerpt: We used systematic multiplex rt-pcr and dna microarray hybridization methods to examine the expression of the genes in the chromosomal regions of 18q21-qter, 8p, and 1p33-pter, which are often decreased in copy number in breast tumors and cell lines derived from breast cancer. We identified dozens of genes in the chromosomal regions whose expression was frequently diminished or lost in breast cancer cell lines that were examined. We confirmed the results by real-time qrt-pcr. We also examined the expression of those genes in the clinical specimens of breast cancer and observed the down-regulation in expression of some of them in the clinical specimens of breast cancer. Those genes included ccbe1, tcf4, np_115536.1, and np_689683.2 in 18q21-qter, and myom2, np_859074, np_001034551, nrg1, phyip (phyhip), q7z2r7, sfrp1, and sox7 in 8p.

Download or read book Identification of Novel Tumor Suppressor Genes in Human Breast Cancer Using Nonsense Mediated MRNA Decay Inhibition NMDI Microarray Analysis written by and published by . This book was released on 2007 with total page 35 pages. Available in PDF, EPUB and Kindle. Book excerpt: This project sought to identify genes that harbor nonsense mutations in breast cancer cell lines that are commonly used as in vitro models in the study of breast cancer biology, with the ultimate aim of identifying novel tumor suppressor genes for sporadic breast cancer. We focused our efforts on the long arm chromosome 22 which is known to undergo LOH in primary breast tumors. Before the NMD-microarray strategy could be undertaken, we very thoroughly characterized chromosome 22q copy number and allelic imbalance in several breast cancer cell lines by integrating publicly available genetic data with empirical data derived from 317K single nucleotide polymorphism (SNP) arrays. MCF-7, T-47D, and MDA-MB-231 breast cancer-derived cell lines were selected for NMD-microarray analysis. Two different regimens for inhibiting NMD were then directly compared for their ability to specifically inhibit NMD while leaving wild-type transcripts unaffected. The improved second-generation NMD protocol was performed and we eagerly await the results of the Affymetrix GeneChip expression arrays so that interrogation of the expression data may begin.

Download or read book A Breast Tumor Suppressor Gene on 8p22 Identification by the Genetic Suppressor Element Approach written by and published by . This book was released on 2002 with total page 10 pages. Available in PDF, EPUB and Kindle. Book excerpt: We are currently investigating a putative tumor suppressor gene (TSG) located at chromosomal band 8p22 and its potential gene targets that are involved in breast cancer. We previously proposed to apply the genetic suppressor element (GSE) approach to the identification of this TSG. Briefly, a library of short gene fragments will be introduced into a cell line which demonstrates suppression of clonogenicity in soft agar with the transfer of chromosome 8. Presumably, the 8p22 TSG is responsible for the suppression of clonogenicity, and the introduction of an "active" GSE from the library into the suppressed cells should inhibit the 8p22 TSG contained in the hybrid cells and allow reversion back to the parental phenotype, the ability to grow in soft agar. Any clones that form will be isolated and further evaluated, as a candidate for the TSG.