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 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 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 Genes and Cancer written by Guy-Joseph Lemamy and published by BoD – Books on Demand. This book was released on 2019-09-11 with total page 127 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is a malignant tumor caused by DNA damage, which leads to uncontrolled cell growth. Tumor progression is locally favored by the mitogenic effects of hormones or growth factors, which stimulate the tumor's growth, or the activation of vascular endothelial growth factor receptor, which induces angiogenesis and leads to metastasis. About 300 out of 25,000 genes that set up the human genome are involved in cancer pathology. These genes are divided into three groups: oncogenes, tumor suppressor genes, and DNA repair genes. Activated oncogenes promote the development of cancer, whereas the tumor suppressor and DNA repair genes have a protective role by respectively inhibiting cell cycle progression and inducing apoptosis, or by repairing DNA damage occurring during the cell cycle. This book discusses the issue of tumor suppressor genes through chapters written by experts using advanced biochemistry, cell, and molecular biology tools. The tumor suppressor genes can be used as markers of risk to identify populations with high risk or targets for cancer treatment and therapeutic resistance. We hope that the work provided in this book will be useful for researchers and students and will increase knowledge of the understanding of cancer and improve its treatment.
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 Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Zack Badanna 1933 written by and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The folder may include clippings, announcements, small exhibition catalogs, and other ephemeral items.
Download or read book HET is a Novel Tumor Suppressor Gene in Human Breast Cancer written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: We have discovered that the nuclear matrix protein HET/SAFB maps to a chromosomal locus on 19pl3 which displays very high loss of heterozygozity (LOH). LOH are hallmarks of tumor suppressor genes, and thus we studied whether HET/SAFB could function as a tumor suppressor gene. Over the last three years we have generated data, which not only support our hypothesis but also allowed us to get further funding to extend our studies. We have confirmed the high LOH rates in a second independent LOH study using microdissected breast tumors. Again, the LOH rates were unusually high (70-80%). We have identified point mutations in the HET/SAFB gene in breast cancer cell lines as well as in tumors but not in the adjacent normal tissue. The reintroduction of a mutated SAFB into cell lines leads to phenotypical changes observed in breast tumors. Furthermore, SAFB expression in breast tumors is associated with aneuploidy, suggesting a possible involvement in chromosomal integrity. Finally, we have recently begun to generate mice models, which will help us to definitely prove that SAFB is involved in tumorigenesis.
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 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 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 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 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 Identification of Novel Breast Cancer Susceptibility Genes and First Steps Towards Mutation specific Cell Culture Models written by Hoda Radmanesh and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
