Download or read book as S y sa al Ir q ya al mun aliq t al mum ras t al ahd f written by and published by . This book was released on with total page 63 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 Andrew K. Godwin and published by . This book was released on 2001 with total page 98 pages. Available in PDF, EPUB and Kindle. Book excerpt: OVCA1 and OVCA2 were first identified by us as candidate tumor suppressor genes, due to the fact that they map to a critical region of frequent allelic loss in breast and ovarian cancer at l7p13.3. Our studies have shown that OVCA1 is mutated in some tumor cell lines, and its protein levels are decreased or lost in nearly 40% of breast and ovarian adenocarcinomas, while OVCA2 appears to be unaffected. Expression of low levels of exogenous OVCA1 results in dramatic growth suppression and decreased levels of cyclin D1. We used a yeast-2-hybrid screen to identify OVCA1-associating proteins. One such protein, RBM8, was identified. Amino acid sequence indicates that RBM8 is a new member of an RNA-binding motif (RBM) family which is highly conserved evolutionarily. RBM8, also know as Y14 has been shown to be a shuttling protein that preferentially associates with spliced mRNA in the nucleus and remains associated with newly exported mRNA in the cytoplasm. Mutational analysis revealed no somatic mutations in ovarian tumor however, our current studies suggest that RBM8 is involved in mRNA export and that its levels may be significantly upregulated in most transformed cells. Overall, our studies indicate that altered expression and/or post-translational modifications of OVCA1 is associated with the development of breast and ovarian tumors and suggest a potentially new mechanism for the inactivation of tumor suppressors in cancer.
Download or read book Identification and Characterization of Candidate Tumor Suppressor Genes Potentially Involved in the Etiology of Ovarian Cancer written by David Charles Schultz and published by . This book was released on 1997 with total page 696 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the last century it has become widely accepted that cancer is a genetic disease. Initiation and progression of cancer results from the accumulation of mutations in at least three classes of cellular genes. In this aspect the genetics of ovarian cancer have remained poorly understood with respect to other diseases. During tumorigenesis, many of the documented changes in cellular DNA involve inactivation of tumor suppressor genes. In this aspect, molecular analyses of ovarian cancer specimens indicate that several tumor suppressor genes may be involved in the etiology of this disease. Loss of heterozygosity for polymorphic markers on a chromosome arm is often indicative of the inactivation of a tumor suppressor on that chromosome based on Knudson's "two-hit" hypothesis. Allelic loss studies in a large series of ovarian tumors identified several candidate tumor suppressor loci on chromosome 9. Mutational analysis of CDKN2A/p16 on 9p21 in ovarian tumors revealed a minor role for the inactivation of this gene in ovarian cancer. Overall, these studies suggest the potential involvement of a gene or genes on chromosome 9q in the progression of this disease.
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 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 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 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 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 Obzor raboty gorodskich bibliotek written by and published by . This book was released on 1967 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Analysis of a Novel Breast Cancer Growth Suppressor Gene on Chromosome 17 written by and published by . This book was released on 1995 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding the genetic basis of cancer will greatly improve our ability to develop more effective therapies. One family of genes involved in cancer is the tumor suppressor genes. We have functional evidence for a new breast cancer suppressor gene on chromosome 17. Transfer of a normal human chromosome 17 results in growth arrest of the MCF7 breast cancer cell line. We are using two approaches to localize the region containing this gene. The first involves the transfer of chromosome 17s containing specific deletions into MCF7 cells followed by our growth arrest assay to determine whether that chromosome contains the suppressor gene. We have determined that the gene lies on chromosome 17q and are now further localizing this gene. In parallel, we are studying loss of heterozygosity (or LOH, which is an indirect indicator of the presence of a suppressor gene) in breast tumors and have identified at least three candidate LOH regions on chromosome 17. Future studies will involve physical mapping of the region containing the suppressor gene, and we provide evidence for our ability to develop region-specific markers. We have also undertaken feasibility studies to determine whether YACs can be used in the MCF7 growth arrest assay.
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 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 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.
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 A Novel Candidate Ovarian Cancer and Melanoma Tumor Suppressor Gene on Chromosome 6q24 3 written by Andrew J. Rice and published by . This book was released on 2002 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of Putative Proto Oncogenes and Tumor Suppressor Genes That Are Transcriptionally Deregulated in Breast Cancer written by and published by . This book was released on 1999 with total page 12 pages. Available in PDF, EPUB and Kindle. Book excerpt: Candidate proto-oncogenes and tumor suppressor genes were previously isolated in a gene expression study involving breast cancer. The present research focus on the characterization of genetic alterations associated with presenilin-2 (PS-2), a gene identified in the gene expression a%alysis. PS-2 has been implicated in the pathogenesis of Alzheimer's disease, but functional studies indicate that the gene plays a role in pathways commonly perturbed in cancer, hence suggesting that PS-2 may be a target for genetic alterations in tumors. PS-2 maps to a chromosomal region for which LOH/deletion in breast tumors has been reported. We found low PS-2 expression in a fraction of breast tumors. In some cases, the reduction in expression can be attributed to deletion at the PS-2 genomic locus. In addition, we identified two sequence alterations in PS-2 which resulted in amino acid substitutions. Both of the alterations were observed to affect the physiological activity of PS-2, but appear not to be contributing to the Alzheimer's phenotype. The alterations may indeed contribute to mammary tumorigenesis and we are in the process of further exploring this possibility.
