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 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 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 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 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 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 Pro Memoria written by and published by . This book was released on 1797 with total page 4 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification of Novel Candidate Tumor Suppressor Genes at 5q and 14q for Multiple Carcinomas by Integrative Genomics and Epigenetics written by Ka Man Ng and published by . This book was released on 2007 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Novel Notch Target Genes in Breast Cancer written by Pavel Goldvasser and published by . This book was released on 2013 with total page 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 Candidate Tumor Suppressor Genes Downregulated by Promoter Hypermethylation in Gastric Carcinogenesis written by Xin Liu and published by . This book was released on 2010 with total page 252 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification of Two Candidate Tumor Suppressor Genes on Chromosome 17p13 3 Assessment of Their Roles in Breast and Ovarian Carcinogenesis written by and published by . This book was released on 1997 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is one of the most common malignancies affecting women in the US. Despite the magnitude of this disease little is known about the molecular events that occur during its development. We have identified a region of less than 30 kbp, on chromosome l7pl3.3 by allelic loss mapping, which is altered in>50% of the breast tumors analyzed. Using positional cloning techniques we have identified a gene, OVCA2, within this region, which we believe may be a tumor suppressor gene.
Download or read book Identification of Transcriptionally Deregulated Genes in Breast Cancer written by Minh Dong To and published by . This book was released on 1998 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
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.
Download or read book Use of Genetic Suppressor Elements to Identify Potential Breast Tumor Suppressor Genes written by Marija Zeremski and published by . This book was released on 1998 with total page 53 pages. Available in PDF, EPUB and Kindle. Book excerpt: ING1 is recently isolated breast cancer candidate tumor suppressor gene. In this study, structure and expression of the mouse ing1 gene were analyzed. Ing1 is transcribed from three differently regulated promoters. Each of the resulting transcripts represents two exons; they share a long common region encoded by a common exon and differ in their 5'-exon sequences encoded by alternative 5'-exons. Three alternative transcripts of ing1 encode two proteins one of which is a truncated version of the other. Protein sequences encoded by mouse and human ing1 are highly conserved. Expression of ing1 mRNA expression correlates with cell proliferation suggesting a connection between cell growth regulation and ing1 expression. Embryonic stem cells with heterozygous deletion of ing1 common exon are prepared as a first step in the generation of ing1 knockout mice. Analysis of ing1 knockout animals should give important information about the role ing1 might have in carcinogenesis.
Download or read book Identification of Novel Candidate Tumor Suppressor Genes Using C Elegans as a Model written by and published by . This book was released on 1999 with total page 7 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular genetic analysis of the model organism Caenorhabditis elegans was used to identify and study mechanisms of action of negative regulators of tyrosine kinase/RAS mediated signal transduction that are candidate tumor suppressors. A homolog of the proto oncogene cbl, SLI- 1, inhibits Ras activation by the epidermal growth factor receptor homolog LET-23. Three functional domains of SLI-1 have been identified. The ARK-i protein kinase was discovered and shown to inhibit signaling by LET-23. New screens for additional negative regulators have identified at several genes that will be molecularly cloned.
