Download or read book Characterization of Two Candidate Tumor Suppressor Genes written by Hau-Yi Paulisally Lo 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 Characterization of Two Candidate Tumor Suppressor Genes written by Hau-yi Lo (Paulisally) and published by . This book was released on 2011 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Functional Characterization of Candidate Tumor Suppressor Genes Localized in the Critical Chromosomal Region 13q14 written by Leticia Serra Barrionuevo 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 Identification and Characterization of Candidate Tumor Suppressor Genes from Chromosomal Region 1p22 in Mantle Cell Lymphomas written by Asha Balakrishnan and published by . This book was released on 2004 with total page 282 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Functional and Epigenetic Characterization of Silenced Candidate Tumor Suppressor Genes in Cancers written by Ching Gee Choi and published by . This book was released on 2012 with total page 306 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 Isolation and Characterization of Candidate Tumor Suppressor Genes written by Michele Genini and published by . This book was released on 1995 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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 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 0 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.

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 Tumor Suppressor Gene and Cancer Stemness Gene in Esophageal Squamous Cell Carcinoma written by Liyi Zhang 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 Tumor Suppressor Gene and Cancer Stemness Gene in Esophageal Squamous Cell Carcinoma" by Liyi, Zhang, 張麗儀, 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: Esophageal squamous cell carcinoma (ESCC), the major histological subtype of esophageal cancer, is one of the most common malignancies with poor prognosis in the world. Despite continued development of diagnosis and treatment, ESCC remains the sixth leading cause of cancer death worldwide. Current treatment regimens in ESCC are often characterized by ineffectiveness and poor selectivity. Therapeutic methods directed at cancer-associated genes or cancer stem cells (CSCs) may be effective approaches to cure this deadly cancer. Therefore, this study aims to identify specific ESCC-related genes and cancer stemness genes which help us to develop new targeted agents to achieving objective, long-lasting therapeutic responses in ESCC. To obtain an accurate overview of genetic changes occurring in ESCC patients, our group performed microarray-based mRNA expression profiling and high-throughout transcriptome sequencing (RNA-Seq) to compare differentially expressed genes between ESCC tumors and their corresponding non-tumorous tissues. Prostate stem cell antigen (PSCA) was considered to be a candidate of primary interest due to significantly reduced expression in both microarray and RNA-Seq data. In this study, we examined the role of PSCA on the pathogenesis of esophageal cancer. Our results showed that PSCA was frequently down-regulated in ESCC. Its expression was negatively regulated by transcription factor SOX5. Also, we provided evidence that down-regulation of PSCA was associated with poor clinical outcomes of patients with ESCC. Both in vitro and in vivo assays revealed that PSCA could arrest cell cycle progression and promote differentiation. To further elucidate the mechanism involved in biological function of PSCA, we performed co-immunoprecipitation and mass spectroscopy to identify proteins that associate with PSCA. This study found that RB1CC1, a key signaling node to regulate cellular proliferation and differentiation, interacted specifically with PSCA both in vitro and in vivo. Binding of PSCA and RB1CC1 in cytoplasm resulted in stabilization and translocation of RB1CC1 into nucleus and then further regulates the crucial cell cycle and differentiation genes. Furthermore, in order to identify the cancer stemness genes specifically expressed in CSCs of ESCC, we utilized gene expression analysis to profile 34 stemness-associated genes in ESCC specimens. Developmental pluripotency associated 4 (DPPA4), a well known pluripotent marker of stem cell, was considered as the best candidate. Our following histopathological study demonstrated that DPPA4 rigorously marked the rare CSCs, in contrast to core stemness factors (OCT4 and SOX2) and previous reported CSC markers (CD90 and CD44), which expressed in a large population of cancer cells. Moreover, the expression of DPPA4 was also found to have prognostic value in ESCC, as the appearance of DPPA4+ cells was significantly associated with poor differentiation, advanced stage and higher incidences of lymph node metastasis. Finally, our functional studies showed that ESCC cells expressing exogenous DPPA4 conferred an enhanced ability to initiate tumor, self-renew, resist chemotherapy and metastasize through lymphatic system. In summary, this study provide evidence indicating that novel tumor suppressor gene PSCA and cancer stemness gene DPPA4 may contribute to the development and pr

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 Mapping identification and characterization of candidate tumour suppressor gene s on the short arm of human chromosome 3 involved in several cancers written by Alonso Martinez and published by . This book was released on 2001 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Transcriptional Regulation and Functional Characterization of the Tumor Suppressor Genes Hugl 1 and Hugl 2 written by and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is a multi-step process in which both the activation of oncogenes and the inactivation of tumor suppressor genes alter the normal cellular programs to a state of proliferation and growth. The regulation of a number of tumor suppressor genes and the mechanism underlying the tumor suppression have been intensively studied. Hugl-1 and Hugl-2, the human homologues of Drosophila lgl are shown to be down-regulated in a variety of cancers including breast, colon, lung and melanoma, but the mechanism responsible for loss of expression is not yet known. The regulation of gene expression is influenced by factors inducing or repressing transcription. The present study was focused on the identification and characterization of the active promoters of Hugl-1 and Hugl-2. Further, the regulation of the promoter and functional consequences of this regulation by specific transcription factors was analyzed. Experiments to delineate the function of the mouse homologue of Hugl-2, mgl2 using transgenic mice model were performed. This study shows that the active promoter for both Hugl-1 and Hugl-2 is located 1000bp upstream of transcription start sites. The study also provides first insight into the regulation of Hugl-2 by an important EMT transcriptional regulator, Snail. Direct binding of Snail to four E-boxes present in Hugl-2 promoter region results in repression of Hugl-2 expression. Hugl-1 and Hugl-2 plays pivotal role in establishment and maintenance of cell polarity in a diversity of cell types and organisms. Loss of epithelial cell polarity is a prerequisite for cancer progression and metastasis and is an important step in inducing EMT in cells. Regulation of Hugl-2 by Snail suggests one of the initial events towards loss of epithelial cell polarity during Snail-mediated EMT. Another important finding of this study is the induction of Hugl-2 expression can reverse the Snail-driven EMT. Inducing Hugl-2 in Snail expressing cells results in the re-expression of epithelial mar.

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 Identification of CDH11 as a Candidate Tumor Suppressor in Retinoblastoma and Characterization of Its Role in Retina and Retinoblastoma written by Mellone Noelene Marchong and published by . This book was released on 2007 with total page 244 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since Kundson's two hit hypothesis of the retinoblastoma tumor susceptibility gene in 1971 and the subsequent cloning of RB1 in 1986 and 1987, pRB has been the highlight of cancer research. It represents the prototypical model for inherited cancers and has since lead to better understanding of cancer genetics. The disease is unique in that its initiating mutational events are known, loss of both alleles of RB1, mutational events 1 and 2 (M1 and M2). Investigation of mutational events, M3-Mn, that lead to its progression will be useful for better understanding of retinoblastoma tumorigenesis, which can ultimately translate to the development of new and better therapeutics that can be used to halt retinoblastoma progression at a very early stage. Loss of chromosomal region 16q22 is a significant genomic change recognized not only in retinoblastoma but in numerous other cancers. Using loss of heterozygosity (LOB) and quantitative multiplex PCR (QM-PCR) techniques on a total of 76 retinoblastoma tumors we were able to narrow down the genomic region of loss on chromosome 16q22. We identified a gene, CDH11, to be a candidate tumor suppressor in retinoblastoma, as it was found to display copy number loss in 58% of 71 tumors and protein expression loss in tumors of both human and murine retinoblastoma. To study the role of cadherin-11 in retinogenesis, I compared developing retinae of Cdh11+/+, Cdh11+/- and Cdh11-/- mouse littermates, and report that Cdh11 plays a subtle role during murine retinogenesis, whereby it supports the development of the retinoblastoma susceptibility cells in the transgenic SV40 large T-antigen mouse model of retinoblastoma (TAg-RB). I also report that retinoblastoma tumors in mice with mutant alleles of Cdh11 grow faster than tumors in mice with normal Cdh11 alleles. These results herein, concur with characteristics identifying tumor suppressor genes. Thus, I provide compelling evidence to support a tumor suppressor role for Cdh11 in retinoblastoma progression.

Download or read book Molecular Characterization of Tumor Suppressor Genes P53 RB and BRCA1 written by Yumay Chen and published by . This book was released on 1997 with total page 406 pages. Available in PDF, EPUB and Kindle. Book excerpt: