Download or read book Characterization of Novel Tumor Suppressor Genes DLC 1 and DLC 2 in Hepatocellular Carcinoma written by Chun-ming Wong (Ph.D.) and published by . This book was released on 2003 with total page 422 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Characterization of Novel Tumor Suppressor Genes DLC 1 and DLC 2 in Hepatocellular Carcinoma written by Chun-Ming Wong and published by Open Dissertation Press. This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Characterization of Novel Tumor Suppressor Genes, DLC-1 and DLC-2, in Hepatocellular Carcinoma" by Chun-ming, Wong, 黃俊銘, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Characterization of Novel Tumor Suppressor Genes, DLC-1 and DLC-2, in Hepatocellular Carcinoma Submitted by Wong Chun-Ming For the degree of Doctor of Philosophy at the University of Hong Kong in December 2003 Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Although the risk factors are well known, the underlying molecular mechanisms contributing to hepatocarcinogenesis are far from clear. Deletions of chromosomal materials are the most frequent genetic alteration found in HCC. Allelic losses in HCC show a non-random pattern, and chromosomes 8p and 13q are two of the most susceptible chromosomal arms. However, critical regions of loss and putative suppressor genes on 8p and 13q have not been firmly identified. Our experimental data indicated that allelic losses on chromosomes 8p and 13q were frequent in HCC and were associated with aggressive tumor phenotypes. In addition, our results showed recurrent losses on the sub-chromosomal regions 8p21.3-22 and 13q12.3. Such recurrent losses suggest the presence of putative tumor suppressor genes, loss of which may be important to HCC development and progression. In search of candidate tumor suppressor genes in these regions, we identified a novel gene DLC-2 (deleted in liver cancer 2) at 13q12.3. DLC-2 shared a high sequence homology with putative tumor suppressor gene DLC-1 at 8p21.3-22. Both DLC-1 and DLC-2 are GTPase activating proteins that activate the intrinsic GTPase activity of RhoA and Cdc42 and switch them off by converting the active GTP-bound state to the inactive GDP-bound state. Several lines of evidence suggest that aberrant activation of Rho proteins is oncogenic. Thus, it is not surprising that DLC-1 and DLC-2 may function as a tumor suppressor. Although we rarely found somatic mutations in the RhoGAP domain of DLC-1 or DLC-2 mRNA, deletion of DLC-1 or DLC-2 locus as revealed by loss of heterozygosity analysis was frequent in human HCC. In addition, DLC-1 and DLC-2 were significantly underexpressed at mRNA levels in primary HCC, suggesting that loss of DLC-1 and DLC-2 functions as a result of downregulated mRNA expression might contribute to hepatocarcinogenesis. Furthermore, DLC-1 promoter methylation was found in 6 (24%) of 25 primary HCCs and in hepatoma cell lines showing loss of DLC-1 mRNA expression. Our results indicated that both genetic and epigenetic alterations play an important role in inactivation of the DLC-1 gene in hepatocarcinogenesis. We also characterized the tumor suppression function of DLC-1 and DLC-2. We noticed that colony formation was significantly inhibited by transient transfection of DLC-1 cDNA into hepatoma cell lines with no DLC-1 expression. Furthermore, stable expression of DLC-1 mRNA successfully suppressed the proliferation, mitogen- independent growth, and anchorage-independent growth capabilities of SMMC-7721 cells. On the other hand, expression of the GAP domain of DLC-2 in mouse fibroblasts sufficiently repressed Ras signaling and Ras-induced cellular transformation. Overall, our findings suggest that DLC-1 and DLC-2 play an important role in hepatocarcinogenesis. An abstract of 439 words DOI: 10.5353/th_b2776853 Subjects: Liver - Cancer - Genetic aspects Antioncogenes

Download or read book Identification and Characterization of a Novel Tumor Suppressor Gene Delected in Liver Cancer 2 Dlc2 written by Ho-Yin Thomas Leung and published by Open Dissertation Press. This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Identification and Characterization of a Novel Tumor Suppressor Gene, Delected in Liver Cancer 2, (DLC2)" by Ho-yin, Thomas, Leung, 梁浩然, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled "Identification and characterization of a novel tumor suppressor gene, deleted in liver cancer 2, (DLC2)" Submitted by Leung Ho Yin, Thomas for the degree of Doctor of Philosophy at The University of Hong Kong in December 2005 The deleted in liver cancer 2 (DLC2) gene, located at chromosome 13q12.3, is a recently identified tumor suppressor gene. The DLC2 gene has striking homology to another tumor suppressor gene, DLC1, located at chromosome 8p22-8p21.3. The DLC2 gene is frequently underexpressed in human hepatocellular carcinoma and its chromosomal region shows frequent deletion. DLC2 encodes a novel RhoGTPase-activating protein (RhoGAP) specific for small RhoGTPases, RhoA and Cdc42. With bioinformatic analysis, we have identified four different isoforms of DLC2, which we named DLC2α, β, γ and δ. Three of the isoforms contain the RhoGAP domain, namely, DLC2α, β and γ. Ectopic expression of these three isoforms in mouse fibroblasts showed cytoplasmic localization. Interestingly, overexpression of these isoforms suppressed the lysophosphatidic acid-induced stress fiber formation in mouse fibroblasts and changed the morphology of the transfected cells from angular and spindle to round. Furthermore, the RhoA pull-down assay demonstrated a remarkable reduction in RhoA activity in the DLC2 transiently transfected cells. In contrast, cells transfected with inactive DLC2 GAP-mutant remained unchanged in cell morphology, actin stress fiber formation, and RhoA activity. HepG2 hepatoma cells stably transfected with the DLC2γ isoform also changed to a round morphology, as in mouse fibroblasts. Significantly, these DLC2γ stable transfectants showed marked suppression in cell proliferation, cell cycle progression, cell motility and transformation, and there was a remarkable reduction in in vivo RhoA activity in these cells. These results suggest that DLC2 exhibits its tumor suppressor functions in vivo as a GTPase activating protein specific for RhoA, exerting its effects in suppression of cytoskeleton reorganization, cell growth, cell migration and transformation. (An abstract of 260 words) DOI: 10.5353/th_b3644505 Subjects: Antioncogenes Liver - Cancer - Genetic aspects

Download or read book Identification and Characterization of a Novel Tumor Suppressor Gene Delected in Liver Cancer 2 DLC2 written by Ho-yin Leung (Ph.D., Thomas) and published by . This book was released on 2005 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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 Characterization of TROP 2 as a Novel Tumor Suppressor Gene in Hepatocellular Carcinoma written by 冼子君 and published by . This book was released on 2018 with total page 132 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Functional Characterization of Novel Tumor Suppressor Galectin 2 in Hepatocellular Carcinoma written by 李家慧 and published by . This book was released on 2015 with total page 53 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Identification and Characterization of Tumor Suppressor Gene and Cancer Stemness Gene in Hepatocellular Carcinoma written by 严倩 and published by . This book was released on 2018 with total page 155 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Identification and Characterization of Novel Genetic Alterations in the Progression of Hepatocellular Carcinoma written by Ming Liu and published by Open Dissertation Press. This book was released on 2017-01-26 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Identification and Characterization of Novel Genetic Alterations in the Progression of Hepatocellular Carcinoma" by Ming, Liu, 劉銘, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally believed that accumulation of irreversible alterations in critical oncogenes and tumor suppressor genes during the long-term inflammation finally leads to the hepatocellular pathogenesis. Although under intensive investigation, the molecular pathogenesis of HCC still remains to be further elucidated. In this study, we aimed to identify novel genetic alterations critical to the pathogenesis of HCC, especially in hot regions with recurrent chromosomal instability. Amplification of broad regions of 8q is one of the most frequent genetic alterations in HCC, suggesting the existence of oncogenes in addition to MYC at 8q24. By screening the publicly available microarray database and clinical samples, we found frequent amplification and overexpression of Serum and Glucocorticoid Kinase 3 (SGK3) in clinical HCC specimens, and SGK3 genomic activation was significantly associated with poor outcome of HCC patients. Functional assays revealed that SGK3 could increase G1/S cell cycle progression, cell survival, clonogenicity, anchorage-independent growth, and tumor formation in nude mice. We provided evidences that SGK3 could promote HCC growth and survival through inactivating GSK3-β and BAD respectively. We also found that expression of SGK3, which like AKT is activated by PI3K/PDK1, has more significance than overexpression of AKT in predicting poor outcome of HCC patients. Our findings suggested the existence of an AKT-independent SGK3 pathway, which may function in parallel with AKT pathway in the pathogenesis of HCC. In addition to large chromosomal alterations, small changes in nucleotides may also make substantial contributions to carcinogenesis. Recent advances in high-throughput deep sequencing technology have provided a powerful tool to understand the whole cancer transcriptome and identify novel genetic alterations related to cancer progression. In this study, we identified a high proportion of allele imbalance in genes related to cellular stress response by sequencing the whole transcriptome of 3 paired HCC tissues. A novel nucleotide variation which resulted in a R438H amino acid change was identified in the coding region of the gene Oxidative Stress Induced Growth Inhibitor 1 (OSGIN1), and the variant 438H form of OSGIN1 was found to be specifically retained in the tumor tissues in a cohort of HCC patients. OSGIN1 was found to be closely associated with chemotherapeutic reagents and exhibited strong tumor suppressive function in HCC by directly inducing cell apoptosis. The wild type OSGIN1 was found to have stronger tumor suppressive function than the variant allele, and this might be due to their different ability to localize to mitochondria. The significantly decreased basal apoptotic index in HCC patients carrying OSGIN1 variant allele and their poor prognosis further suggested that the specific retention of 438H OSGIN1 might be important in HCC progression. In summary, we found a frequently amplified oncogenic SGK3 signaling pathway, as well as the allele-specific imbalance of tumor suppressive OSGIN1 in the pathogenesis of HCC. Further characterization of their mechanisms in hepatocarcinogenesis may help provide novel prognostic biomarkers and therapeutic targets in HCC treatment. DOI: 10.5353/th_b5177316

Download or read book Transcriptional Regulation and Functional Characterization of the Tumor Suppressor Genes Hugl 1 and Hugl 2 written by Anubha Kashyap and published by . This book was released on 2008 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Functional Characterization of Tumor Suppressor Genes SORBS3 and SH2D4A with Regard to STAT Signaling in Hepatocellular Carcinoma written by Carolin Plöger and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Future Aspects of Tumor Suppressor Gene written by Yue Cheng and published by BoD – Books on Demand. This book was released on 2013-04-10 with total page 234 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumor suppressor genes (TSGs) and their signaling networks are fast growing areas in current biomedical science. These groups of genes, which are not limited to tumor suppression, play critical roles in many cellular activities. This book, "Future Aspects of Tumor Suppressor Genes", contains some fascinating fields, from basic to translational researches, in recent TSG studies. For example, several TSG signaling pathways are addressed in this book, and both mouse and Drosophila models used for the exploration of these genes are described based on the experimental evidence. A detailed review for current knowledge of microRNA studies in the regulation of tumor growth is introduced. Additionally, how natural compounds interfere with the progression of cancer development via TSG pathways is systemically summarized. Recent progresses in cell reprogramming and stemness transition processes regulated by TSG pathways are also included in this book.

Download or read book Identification and Characterization of Novel Tumor associated Genes in Liver Cancer written by 洪偉翔 and published by . This book was released on 2010 with total page 98 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Tumor Suppressor Genes written by Wafik S. El-Deiry and published by Humana PressInc. This book was released on 2003-04-21 with total page 657 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumor Suppressor Genes provides a timely foundation for understanding cancer. It provides critical information to rapidly gain appreciation of important tumor suppressor genes in human cancer as well as modern methods for their discovery, analysis, and clinical application. It covers all the known tumor suppressor pathways and provides key information on the road to their discovery and use in cancer therapy. Volume I of this text, educates the reader on the relevance of known tumor suppressor genes (TSGs) and the relevance of the biochemical pathways they regulate to human cancer. The reader has an opportunity in volume I to access state-of-the-art protocols that have been successful in the identification of TSGs in the past and which can be applied to isolate novel TSGs. With a novel TSG at hand, the reader has an opportunity in volume II to explore the cell biology and biochemical function of the encoded protein, as well as its physiological role in-vivo. Also contained in volume II, strategies for the use of information on TSGs to develop diagnostic and therapeutic strategies for cancer are presented. This two-volume text brings together the world's most expert researchers in the identification and characterization of tumor suppressor genes.

Download or read book Identification and Characterization of a Putative Tumor Suppressor Gene Akr7a3 in Hepatocellular Carcinoma written by Kwok-Kei Chow and published by . This book was released on 2017-01-26 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Dissertation Abstracts International written by and published by . This book was released on 2008 with total page 980 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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.