Página 1 dos resultados de 3878 itens digitais encontrados em 0.023 segundos

Constitutional Haploinsufficiency of Tumor Suppressor Genes in Mentally Retarded Patients With Microdeletions in 17p13.1

KREPISCHI-SANTOS, A. C. V.; RAJAN, D.; TEMPLE, I. K.; SHRUBB, V.; CROLLA, J. A.; HUANG, S.; BEAL, S.; OTTO, P. A.; CARTER, N. P.; VIANNA-MORGANTE, A. M.; ROSENBERG, C.
Fonte: KARGER Publicador: KARGER
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.2%
Chromosome microdeletions or duplications are detected in 10-20% of patients with mental impairment and normal karyotypes. A few cases have been reported of mental impairment with microdeletions comprising tumor suppressor genes. By array-CGH we detected 4 mentally impaired individuals carrying de novo microdeletions sharing an overlapping segment of similar to 180 kb in 17p13.1. This segment encompasses 18 genes, including 3 involved in cancer, namely KCTD11/REN, DLG4/PSD95, and GPS2. Furthermore, in 2 of the patients, the deletions also included TP53, the most frequently inactivated gene in human cancers. The 3 tumor suppressor genes KCTD11, DLG4, and GPS2, in addition to the GABARAP gene, have a known or suspected function in neuronal development and are candidates for causing mental impairment in our patients. Among our 4 patients with deletions in 17p13.1, 3 were part of a Brazilian cohort of 300 mentally retarded individuals, suggesting that this segment may be particularly prone to rearrangements and appears to be an important cause (similar to 1%) of mental retardation. Further, the constitutive deletion of tumor suppressor genes in these patients, particularly TP53, probably confers a significantly increased lifetime risk for cancer and warrants careful oncological surveillance of these patients. Constitutional chromosome deletions containing tumor suppressor genes in patients with mental impairment or congenital abnormalities may represent an important mechanism linking abnormal phenotypes with increased risks of cancer. Copyright (C) 2009 S. Karger AG...

Análise do status somático dos genes MEN1, AIP e p27Kip1 em tumores de pacientes com neoplasia endócrina múltipla tipo 1; Analysis of the status of somatic and p27Kip1 genes in tumors from patients with multiple endocrine neoplasia type 1

Moraes, Michelle Buscarilli de
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 06/06/2012 PT
Relevância na Pesquisa
56.21%
Aproximadamente 80% dos casos com Neoplasia endócrina múltipla tipo 1 (NEM1) possuem mutações germinativas no gene supressor de tumor MEN1, que os predispõem a tumores nas glândulas paratireóides, pâncreas endócrino e hipófise, além de outros tumores não endócrinos. A tumorigênese dos mais de 20 diferentes tipos de neoplasias já descritas na NEM1 ocorre pela presença da mutação germinativa MEN1 associadas a um segundo evento mutacional nas células desses tecidos, levando à perda de heterozigose (LOH) do locus do gene MEN1 (11q13) e à inativação da proteína supressora de tumor codificada por esse gene, a proteína MENIN. Recentemente, mutações germinativas em outros genes foram descritas em casos com NEM1 sem mutações no gene MEN1. Esses novos genes (CDKN1A, CDKN1B, CDNK2B e CDKN2C) codificam proteínas envolvidas no controle do ciclo celular (p21, p27, p15 e p18), chamadas proteínas inibidoras de quinases dependentes de ciclinas. Outro gene, chamado AIP, que codifica uma proteína chaperona de mesmo nome, também foi recentemente descrito associado à NEM1. Esses trabalhos descreveram o papel desses novos genes na NEM1, em nível germinativo, entretanto não esclareceu se esses novos genes estão inativados nos tumores de pacientes com NEM1 com mutação MEN1. O presente estudo investigou...

Caracterização da expressão de microRNAS em carcinoma de mama triplo negativo; Characterization of the expression of microRNAs in triple negative breast carcinoma

Calvano Filho, Carlos Marino Cabral
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 22/07/2014 PT
Relevância na Pesquisa
56.09%
INTRODUÇÃO: Os microRNAs (miRNAs) são uma classe de pequenas moléculas não codificadoras de proteínas que regulam a expressão gênica durante a etapa de tradução. Esta regulação é feita pelo pareamento de bases com o mRNA-alvo (RNA mensageiro), resultando na supressão da tradução ou na clivagem do mRNA. A depender se os miRNAs têm como alvo genes supressores de tumor ou oncogenes, eles podem atuar como supressores tumorais ou oncogenes. A imunoistoquímica triplo negativa, no câncer de mama, é, comumente, utilizada como substituto clínico para identificação dos tumores basaloides, que se caracterizam pela expressão de genes epiteliais basais, sendo associados a menores taxas de sobrevida livre de doença e sobrevida global. O câncer de mama triplo negativo faz com que seja necessária a descoberta de marcadores moleculares que possam servir de alvos terapêuticos ou, pelo menos, que sirvam como marcadores preditivos da resposta aos quimioterápicos. OBJETIVO: avaliar a expressão de microRNAs, por PCR em tempo real, no carcinoma mamário ductal invasivo (CDI) triplo negativo. MÉTODOS: Foram avaliados materiais em parafina de tumor de 31 pacientes com as seguintes características: carcinoma invasivo de mama...

Caracterização da expressão de microRNAs em carcinoma de mama receptores hormonais positivos e HER-2 negativo; Caracterização da expressão de microRNAs em carcinoma de mama receptores hormonais positivo e HER-2 negativo

Mendes, Daniele Carvalho Calvano
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 27/01/2015 PT
Relevância na Pesquisa
56.06%
Introdução: O câncer de mama é, em sua essência, uma doença genética. O acúmulo de alterações moleculares no genoma das células somáticas é a base para a progressão do câncer. Além de ter biologia natural mais favorável, os tumores com alta expressão de receptores de estrogênio têm terapia-alvo bem estabelecida. Apesar disso, as pacientes podem apresentar resistência medicamentosa, recidiva e óbito. Os microRNAs (miRNAs) são uma classe de pequenas moléculas não codificadoras de proteínas que regulam a expressão gênica durante a etapa de tradução. Esta regulação é feita pelo pareamento de bases com o mRNA-alvo (RNA mensageiro), resultando na supressão da tradução ou na clivagem do mRNA. Se os miRNAs têm como alvo genes supressores de tumor ou oncogenes, podem atuar como supressores tumorais ou oncogenes. OBJETIVO: avaliar a expressão de microRNAs, por PCR em tempo real, no carcinoma mamário ductal invasivo (CDI) com receptores hormonais positivos e HER-2 negativo (luminal A). MÉTODOS: Foram avaliados materiais em parafina de 33 pacientes com tumores luminal A, bem como tecido mamário histologicamente normal. Foram utilizados kit para extração de RNA de amostras fixadas e parafinadas - miRNeasy FFPE; kit para síntese de cDNA - miScript II RT; kit miScript SYBR Green PCR e miScript miRNA PCR Arrays para análise de 84 sequências de miRNA de câncer humano. Analisaram-se dados clínicos...

Effect of Regucalcin on the expression of oncogenes and tumor suppressor genes in prostate cell lines

Vaz, Cátia Alexandra Vicente
Fonte: Universidade da Beira Interior Publicador: Universidade da Beira Interior
Tipo: Dissertação de Mestrado
Publicado em //2010 ENG
Relevância na Pesquisa
56.17%
Regucalcin (RGN) is a calcium-binding protein playing an important role in maintenance of intracellular calcium homeostasis. Because of its diminished expression with aging it is also designated Senescence-marker-protein (SMP30). In addition, RGN suppresses cell proliferation, inhibits expression of oncogenes, and increases the expression of tumor suppressor genes in hepatoma cell lines. Very recently, our research group demonstrated that RGN expression is diminished in prostate cancer tissues, what suggests that RGN may have a protective role against carcinogenesis and, consequently, loss of regucalcin expression may contribute to tumor development. The present project aims to characterize RGN expression in prostate tissues and cell-lines and to determine the role of RGN on the expression of oncogenes and tumour suppressor genes in neopasic and non-neoplasic prostate cells. The expression of RGN in rat prostate at different post-natal ages determined by quantitative PCR analysis showed a significant increase at 3M old rats, maintaining their expression in 6M-old animals and diminishing in the following stages. In this report, we confirmed RGN protein expression in human cancer prostate tissues, and cells lines by Imunohistochemistry and Western Blot...

Immunoexpression of tumor suppressor genes p53, p21WAF1/CIP1 and p27KIP1 in humam astrocystic tumors

Faria,Mário Henrique Girão; Patrocínio,Régia Maria do Socorro Vidal do; Moraes Filho,Manoel Odorico de; Rabenhorst,Silvia Helena Barem
Fonte: Academia Brasileira de Neurologia - ABNEURO Publicador: Academia Brasileira de Neurologia - ABNEURO
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2007 EN
Relevância na Pesquisa
66.07%
The aim of the present study was to evaluate the tumor suppressor genes p53, p21WAF1/CIP1 and p27KIP1 expression in astrocytic tumors, correlating the findings with the histopathological grade (WHO). An immunohistochemical study of the p53, p21 and p27 proteins using the streptavidin-biotin-peroxidase method was performed in fifty-five astrocytomas (13 grade I, 14 grade II, 7 grade III and 21 grade IV) and five samples of non-tumor brain tissue (negative control). p53 positive indices (PI) and labeling indices (LI) showed tendency to increase according to malignant progression. The nuclear expression of p27 presented similar inclination, except for the PI reduction verified in grade IV tumors. Otherwise, the cytoplasmic p27 staining was more evident between high-grade tumors (III and IV). p53 and nuclear p27 expression was correlated with the histological classification (p<0.01; test H). On the other hand, p21 indices revealed a propensity to reduction in agreement with malignant evolution of the astrocytic tumors, except for high scores observed in grade IV tumors. The non-tumor samples did not show any expression of these proteins. These results indicated the p53 mutation as an initial, relevant and potentially predictor of tumor progression event in astrocytomas...

Hypomethylation of tumor suppressor genes in odontogenic myxoma

Moreira,Paula Rocha; Cardoso,Fabiano Pereira; Brito,João Artur Ricieri; Batista,Aline Carvalho; Gomes,Carolina Cavaliéri; Gomez,Ricardo Santiago
Fonte: Fundação Odontológica de Ribeirão Preto Publicador: Fundação Odontológica de Ribeirão Preto
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2011 EN
Relevância na Pesquisa
66.18%
Odontogenic myxoma (OM) is an ectomesenchymal benign odontogenic tumor characterized by spindle or stellate-shaped cells embedded in an abundant myxoid or mucoid extracellular matrix. DNA methylation is characterized by the addition of methyl groups in cytosines within CpG islands in the promoter gene. DNA methylation can decrease the expression of tumor suppressor genes and contribute to the development of neoplastic lesions. The aim of study was to evaluate the methylation pattern of the tumor suppressor genes P16 (CDKN2A), P21 (CDKN1A), P27 (CDKN1B), P53 (TP53) and RB1 in OM and dental pulp. Methylation was evaluated using methylation-specific polymerase chain reaction (PCR). The transcription was studied in some cases by using reverse transcription quantitative PCR. A higher frequency of unmethylated P27, P53, and RB1 samples was observed in the OM when compared with the dental pulp. OM expressed mRNA of all the genes evaluated. Considering all the samples together, the expression of Rb was higher in the unmethylated samples compared with the partially methylated samples. This investigation revealed hypomethylation of the genes P27, P53, and RB1 in OM. In addition, methylation of tumor suppressor genes was found to be an usual event in normal dental pulp.

The role of HER2/neu, BCL2, p53 genes and proliferating cell nuclear protein as molecular prognostic parameters in localized prostate carcinoma

Fonseca,Gilvan Neiva; Srougi,Miguel; Leite,Katia Ramos Moreira; Nesrallah,Luciano João; Ortiz,Valdemar
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/05/2004 EN
Relevância na Pesquisa
66.07%
CONTEXT: Prostate cancer is the most frequent solid genitourinary neoplasm in men. Involvement of several genes has been described in the promotion and progression of prostate carcinoma. OBJECTIVE: To study the expression of the oncogenes HER2/neu and BCL2, tumor suppressor gene p53 and the tumor proliferation rate in 150 radical prostatectomy specimens, in order to define their role as prognostic parameters in localized prostate cancer. TYPE OF STUDY: Prospective study. SETTING: Universidade Federal de São Paulo and Hospital Sírio Libanês, Sao Paulo PARTICIPANTS: One hundred and fifty men who were submitted to radical prostatectomy between August 1997 and August 1998, for localized prostate cancer. MAIN MEASUREMENTS: All specimens underwent evaluation in their entirety, to determine tumor volume percentage, tumor extent and Gleason score. Immunohistochemistry was performed to determine gene expression using anti- HER2/neu, BCL2 and p53 antibodies, and proliferating cell nuclear antigen. The chi-squared test was used for correlation between gene expression, proliferative activity and histological variables. RESULTS: Thirty percent of the cases were p53 positive. There was positive correlation between p53 expression and tumor stage. The p53 expression was 22.9% and 42.6% for pT2 and pT3 tumors...

Increased Tumorigenesis Associated with Loss of the Tumor Suppressor Gene Cadm1

van der Weyden, Louise; Arends, Mark J; Rust, Alistair G; McIntyre, Rebecca E; Poulogiannis, George; Adams, David J
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
66.02%
Background: CADM1 encodes an immunoglobulin superfamily (IGSF) cell adhesion molecule. Inactivation of CADM1, either by promoter hypermethylation or loss of heterozygosity, has been reported in a wide variety of tumor types, thus it has been postulated as a tumor suppressor gene. Findings: We show for the first time that Cadm1 homozygous null mice die significantly faster than wildtype controls due to the spontaneous development of tumors at an earlier age and an increased tumor incidence of predominantly lymphomas, but also some solid tumors. Tumorigenesis was accelerated after irradiation of Cadm1 mice, with the reduced latency in tumor formation suggesting there are genes that collaborate with loss of Cadm1 in tumorigenesis. To identify these co-operating genetic events, we performed a Sleeping Beauty transposon-mediated insertional mutagenesis screen in Cadm1 mice, and identified several common insertion sites (CIS) found specifically on a Cadm1-null background (and not wildtype background). Conclusion: We confirm that Cadm1 is indeed a bona fide tumor suppressor gene and provide new insights into genetic partners that co-operate in tumorigenesis when Cadm1-expression is lost.

Characterisation and screening for mutations of the growth arrest-specific 11 (GAS11) and C16orf3 genes at 16q24.3 in breast cancer

Whitmore, S.; Settasatian, C.; Crawford, J.; Lower, K.; McCallum, B.; Seshadri, R.; Cornelisse, C.; Moerland, E.; Cleton-Jansen, A.M.; Tipping, A.; Mathew, C.; Savnio, M.; Savoia, A.; Verlander, P.; Auerbach, A.; Van Berkel, C.; Pronk, J.; Doggett, N.; Ca
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Publicado em //1998 EN
Relevância na Pesquisa
66.11%
Loss of heterozygosity involving the long arm of chromosome 16 is a frequent event seen in a number of human carcinomas, including breast, prostate, hepatocellular, and ovarian cancers. A region found to be commonly deleted in breast and prostate carcinomas is located at 16q24.3, which suggests the presence of a tumor suppressor gene that may be altered in these two malignancies. A detailed physical and transcription map of this region that includes the loci defining the smallest region of deletion has been constructed. This report describes the characterization of a transcript located in this region, the growth arrest-specific 11 (GAS11) gene, which was viewed as a potential tumor suppressor gene due to the expression of its mouse homolog specifically during growth arrest. The gene consists of 11 exons spanning approximately 25 kb. Northern blot analysis identified two ubiquitously expressed mRNAs of 3.4 and 1.8 kb produced by the use of alternative polyadenylation sites. Another gene,C16orf3(chromosome 16 open reading frame 3), was found to lie within intron 2 ofGAS11.This gene appears intronless, is transcribed in the orientation opposite to that ofGAS11,and is expressed at low levels. These genes were examined for mutations in breast tumor DNA...

FBXO31 is the chromosome 16q24.3 senescence gene, a candidate breast tumor suppressor, and a component of an SCF complex

Kumar, R.; Neilsen, P.; Crawford, J.; McKirdy, R.; Lee, J.; Powell, J.; Saif, Z.; Martin, J.; Lombaerts, M.; Cornelisse, C.; Cleton-Jansen, A.M.; Callen, D.
Fonte: Amer Assoc Cancer Research Publicador: Amer Assoc Cancer Research
Tipo: Artigo de Revista Científica
Publicado em //2005 EN
Relevância na Pesquisa
76.05%
A BAC located in the 16q24.3 breast cancer loss of heterozygosity region was previously shown to restore cellular senescence when transferred into breast tumor cell lines. We have shown that FBXO31, although located just distal to this BAC, can induce cellular senescence in the breast cancer cell line MCF-7 and is the likely candidate senescence gene. FBXO31 has properties consistent with a tumor suppressor, because ectopic expression of FBXO31 in two breast cancer cell lines inhibited colony growth on plastic and inhibited cell proliferation in the MCF-7 cell line. In addition, compared with the relative expression in normal breast, levels of FBXO31 were down-regulated in breast tumor cell lines and primary tumors. FBXO31 was cell cycle regulated in the breast cell lines MCF-10A and SKBR3 with maximal expression from late G2 to early G1 phase. Ectopic expression of FBXO31 in the breast cancer cell line MDA-MB-468 resulted in the accumulation of cells at the G1 phase of the cell cycle. FBXO31 contains an F-box domain and is associated with the proteins Skp1, Roc-1, and Cullin-1, suggesting that FBXO31 is a component of a SCF ubiquitination complex. We propose that FBXO31 functions as a tumor suppressor by generating SCFFBXO31 complexes that target particular substrates...

ZNF652, a novel zinc finger protein, interacts with the putative breast tumor suppressor CBFA2T3 to repress transcription

Kumar, R.; Manning, J.; Spendlove, H.; Kremmidiotis, G.; McKirdy, R.; Lee, J.; Millband, D.; Cheney, K.; Stampfer, M.; Dwivedi, P.; Morris, H.; Callen, D.
Fonte: Amer Assoc Cancer Research Publicador: Amer Assoc Cancer Research
Tipo: Artigo de Revista Científica
Publicado em //2006 EN
Relevância na Pesquisa
75.98%
The transcriptional repressor CBFA2T3 is a putative breast tumor suppressor. To define the role of CBFA2T3, we used a segment of this protein as bait in a yeast two-hybrid screen and identified a novel uncharacterized protein, ZNF652. In general, primary tumors and cancer cell lines showed lower expression of ZNF652 than normal tissues. Together with the location of this gene on the long arm of chromosome 17q, a region of frequent loss of heterozygosity in cancer, these results suggest a possible role of ZNF652 in tumorigenesis. In silico analysis of this protein revealed that it contains multiple classic zinc finger domains that are predicted to bind DNA. Coimmunoprecipitation assays showed that ZNF652 strongly interacts with CBFA2T3 and this interaction occurs through the COOH-terminal 109 amino acids of ZNF652. In contrast, there was a weak interaction of ZNF652 with CBFA2T1 and CBFA2T2, the other two members of this ETO family. Transcriptional reporter assays further confirmed the strength and selectivity of the ZNF652-CBFA2T3 interaction. The transcriptional repression of growth factor independent-1 (GFI-1), a previously characterized ETO effector zinc finger protein, was shown to be enhanced by CBFA2T1, but to a lesser extent by CBFA2T2 and CBFA2T3. We therefore suggest that each of the various gene effector zinc finger proteins may specifically interact with one or more of the ETO proteins to generate a defined range of transcriptional repressor complexes.; Raman Kumar...

Sequencing, transcript identification, and quantitative gene expression profiling in the breast cancer loss of heterozygosity region 16q24.3 reveal three potential tumor-suppressor genes

Powell, J.; Gardner, A.; Bais, A.; Hinze, S.; Baker, E.; Whitmore, S.; Crawford, J.; Kochetkova, M.; Spendlove, H.; Doggett, N.; Sutherland, G.; Callen, D.; Kremmidiotis, G.
Fonte: Academic Press Inc Publicador: Academic Press Inc
Tipo: Artigo de Revista Científica
Publicado em //2002 EN
Relevância na Pesquisa
76.1%
Loss of heterozygosity (LOH) of chromosome 16q24.3 is a common genetic alteration observed in invasive ductal and lobular breast carcinomas. We constructed a physical map and generated genomic DNA sequence data spanning 2.4 Mb in this region. Detailed in silico and in vitro analyses of the genomic sequence data enabled the identification of 104 genes. It was hypothesized that tumor-suppressor genes would exhibit marked mRNA expression variability in a panel of breast cancer cell lines as a result of downregulation due to mutation or hypermethylation. We examined the mRNA expression profiles of the genes identified at 16q24.3 in normal breast, a normal breast epithelial cell line, and several breast cancer cell lines exhibiting 16q24.3 LOH. Three of the genes, CYBA, Hs.7970, and CBFA2T3, exhibited variability ten times higher than the baseline. The possible role of these genes as tumor suppressors is discussed.; Jason A. Powell, Alison E. Gardner, Anthony J. Bais, Susan J. Hinze, Elizabeth Baker, Scott Whitmore, Joanna Crawford, Marina Kochetkova, Hayley E. Spendlove, Norman A. Doggett, Grant R. Sutherland, David F. Callen, and Gabriel Kremmidiotis

Myb-binding protein 1A (MYBBP1A) is essential for early embryonic development, controls cell cycle and mitosis, and acts as a tumor suppressor

Mori, S.; Bernardi, R.; Laurent, A.; Resnati, M.; Crippa, A.; Gabrieli, A.; Keough, R.; Gonda, T.J.; Blasi, F.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
Relevância na Pesquisa
65.92%
MYBBP1A is a predominantly nucleolar transcriptional regulator involved in rDNA synthesis and p53 activation via acetylation. However little further information is available as to its function. Here we report that MYBBP1A is developmentally essential in the mouse prior to blastocyst formation. In cell culture, down-regulation of MYBBP1A decreases the growth rate of wild type mouse embryonic stem cells, mouse embryo fibroblasts (MEFs) and of human HeLa cells, where it also promotes apoptosis. HeLa cells either arrest at G2/M or undergo delayed and anomalous mitosis. At mitosis, MYBBP1A is localized to a parachromosomal region and gene-expression profiling shows that its down-regulation affects genes controlling chromosomal segregation and cell cycle. However, MYBBP1A down-regulation increases the growth rate of the immortalized NIH3T3 cells. Such Mybbp1a down-regulated NIH3T3 cells are more susceptible to Ras-induced transformation and cause more potent Ras-driven tumors. We conclude that MYBBP1A is an essential gene with novel roles at the pre-mitotic level and potential tumor suppressor activity.; Jennifer L. Marino, Vivienne M. Moore, Kristyn J. Willson, Alice Rumbold, Melissa J. Whitrow, Lynne C. Giles, Michael J. Davies

Promoter methylation status of tumor suppressor and tumor-related genes in neoplastic and non-neoplastic gastric epithelia

Tamura, G.
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
ENG
Relevância na Pesquisa
66.22%
A number of tumor suppressor and tumorrelated genes exhibit promoter hypermethylation with resulting gene silencing in human cancers. In addition, several gene promoters have also been shown to become hypermethylated in non-neoplastic cells during aging. To assess the physiological consequence and clinical significance of gene promoter methylation in gastric epithelia, our laboratory has studied the methylation status of tumor suppressor and tumor-related genes, including APC, DAP-kinase, DCC, E-cadherin, GSTP1, hMLH1, p16, PTEN, RASSF1A, RUNX3 and TSLC1, in neoplastic and non-neoplastic gastric epithelia. The tumor suppressor and tumor-related genes, except APC, were generally unmethylated in non-neoplastic gastric epithelia obtained from younger individuals. The frequencies of methylation increased with age to varying degrees in various genes, although GSTP1 and PTEN methylation was completely absent in both neoplastic and non-neoplastic gastric epithelia. The methylation frequencies in each gene were found to be comparable in neoplastic and non-neoplastic gastric epithelia, except the methylation of RUNX3 and TSLC1, which was mostly cancer-specific (P<0.01). When methylation frequencies were compared between non-neoplastic gastric epithelia from cancer-bearing and non-cancerbearing stomachs...

The PISSLRE Gene: structure, exon skipping, and exclusion as tumor suppressor in breast cancer

Crawford, J.; Ianzano, L.; Savino, M.; Whitmore, S.; Cleton-Jansen, A.M.; Settasatian, C.; d'Apolito, M.; Seshadri, R.; Pronk, J.; Auerbach, A.; Verlander, P.; Mathew, C.; Tipping, A.; Doggett, N.; Zelante, L.; Callen, D.; Savoia, A.
Fonte: ACADEMIC PRESS INC Publicador: ACADEMIC PRESS INC
Tipo: Artigo de Revista Científica
Publicado em //1999 EN
Relevância na Pesquisa
76.04%
In sporadic breast cancer, loss of heterozygosity (LOH) frequently occurs in three discrete regions of the long arm of chromosome 16q, the most telomeric of which is located at 16q24.3. Among the genes mapped to this region,PISSLREis a plausible candidate tumor suppressor gene. It codes for a putative cyclin-dependent kinase that, as with other members of this family, is likely to be involved in regulating the cell cycle and therefore may have a role in oncogenesis. We characterized the genomic structure ofPISSLREand found that the splicing of this gene is complex. A variety of different transcripts were identified, including those due to cryptic splice sites, exon skipping, insertion of intronic sequences, and exon scrambling. The last phenomenon was observed in a rarePISSLREtranscript in which exons are joined at a nonconsensus splice site in an order different from that predicted by the genomic sequence. To screen thePISSLREgene in breast tumors with ascertained LOH at 16q24.3, we have analyzed each exon by single-strand conformational polymorphism. No variation was found in the coding sequence, leading us to conclude that another tumor suppressor must be targeted by LOH in sporadic breast cancer.; http://www.elsevier.com/wps/find/journaldescription.cws_home/622838/description#description; Joanna Crawford...

CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer loss of heterozygosity region at 16q24.3

Kochetkova, M.; McKenzie, O.; Bais, A.; Martin, J.; Secker, G.; Seshadri, R.; Powell, J.; Hinze, S.; Gardner, A.; Spendlove, H.; O'Callaghan, N.; Cleton-Jansen, A.M.; Cornelisse, C.; Whitmore, S.; Crawford, J.; Kremmidiotis, G.; Sutherland, G.; Callen, D.
Fonte: Amer Assoc Cancer Research Publicador: Amer Assoc Cancer Research
Tipo: Artigo de Revista Científica
Publicado em //2002 EN
Relevância na Pesquisa
76.1%
Numerous cytogenetic and molecular studies of breast cancer have identified frequent loss of heterozygosity (LOH) of the long arm of human chromosome 16. On the basis of these data, the likely locations of breast cancer tumor suppressor genes are bands 16q22.1 and 16q24.3. We have mapped the CBFA2T3 (MTG16) gene, previously cloned as a fusion partner of the AML1 protein from a rare (16;21) leukemia translocation, to the 16q24.3 breast cancer LOH region. The expression of CBFA2T3 was significantly reduced in a number of breast cancer cell lines and in primary breast tumors, including early ductal carcinomas in situ, when compared with nontransformed breast epithelial cell lines and normal breast tissue. Reintroduction of CBFA2T3 into different breast tumor derived cell lines with decreased expression of this gene reduced colony growth on plastic and in soft agar. CBFA2T3 was shown to function as a transcriptional repressor when tethered to the GAL4 DNA-binding domain in a reporter gene assay and, therefore, has the potential to be a transcriptional repressor in normal breast epithelial cells. Taken together, these findings suggest that CBFA2T3 is a likely candidate for the breast cancer tumor suppressor gene that is the target for the frequent 16q24 LOH in breast neoplasms.; Marina Kochetkova...

MICRORNA-193B FUNCTIONS AS A TUMOR SUPPRESSOR IN MALIGNANT MELANOMA

Chen, Jiamin
Fonte: Quens University Publicador: Quens University
Tipo: Tese de Doutorado
EN; EN
Relevância na Pesquisa
65.99%
Cutaneous melanoma is an increasingly common skin cancer characterized by aggressive metastatic growth and poor prognosis. The mechanisms behind melanoma progression are not fully understood, but emerging evidence suggests that a group of newly discovered small regulatory RNAs, named microRNAs (miRNAs), plays an important role. miRNAs are ~ 22 nucleotide single strand non-coding RNAs that post-transcriptionally regulate gene expression by binding to target messenger RNAs (mRNAs), leading to mRNA degradation and translation inhibition. Abnormal expression of miRNAs has been observed in human malignancies and is associated with tumorigenesis. The main goals of this thesis are to investigate miRNA dysregulation in melanoma and to identify potential miRNAs involved in melanoma pathogenesis. Initially, the expression of 470 miRNAs was profiled in 8 metastatic melanoma and 8 benign nevus tissue samples. We discovered unique miRNA expression profiles and identified differentially expressed miRNAs in melanomas as compared to nevi. miR-193b was one of the most significantly downregulated miRNAs in melanoma, and its function and regulatory targets were unknown. Subsequently, in vitro functional studies revealed that ectopic expression of miR-193b in melanoma cells drastically repressed cell proliferation and migration. Although it does not directly induce apoptosis in melanoma cells...

Effect of Regucalcin on the expression of oncogenes and tumor suppressor genes in prostate cell lines; Influência da Regucalcina na expressão de oncogenes e genes supressores de tumor em linhas celulares de próstata

Vaz, Cátia Alexandra Vicente
Fonte: Universidade da Beira Interior Publicador: Universidade da Beira Interior
Tipo: Dissertação de Mestrado
Publicado em //2010 ENG
Relevância na Pesquisa
56.18%
Regucalcin (RGN) is a calcium-binding protein playing an important role in maintenance of intracellular calcium homeostasis. Because of its diminished expression with aging it is also designated Senescence-marker-protein (SMP30). In addition, RGN suppresses cell proliferation, inhibits expression of oncogenes, and increases the expression of tumor suppressor genes in hepatoma cell lines. Very recently, our research group demonstrated that RGN expression is diminished in prostate cancer tissues, what suggests that RGN may have a protective role against carcinogenesis and, consequently, loss of regucalcin expression may contribute to tumor development. The present project aims to characterize RGN expression in prostate tissues and cell-lines and to determine the role of RGN on the expression of oncogenes and tumour suppressor genes in neopasic and non-neoplasic prostate cells. The expression of RGN in rat prostate at different post-natal ages determined by quantitative PCR analysis showed a significant increase at 3M old rats, maintaining their expression in 6M-old animals and diminishing in the following stages. In this report, we confirmed RGN protein expression in human cancer prostate tissues, and cells lines by Imunohistochemistry and Western Blot...

Oncogene-mediated downregulation of RECK, a novel transformation suppressor gene

Sasahara,R.M.; Takahashi,C.; Sogayar,M.C.; Noda,M.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/1999 EN
Relevância na Pesquisa
56.14%
The RECK gene was initially isolated as a transformation suppressor gene encoding a novel membrane-anchored glycoprotein and later found to suppress tumor invasion and metastasis by regulating matrix metalloproteinase-9. Its expression is ubiquitous in normal tissues, but undetectable in many tumor cell lines and in fibroblastic lines transformed by various oncogenes. The RECK gene promoter has been cloned and characterized. One of the elements responsible for the oncogene-mediated downregulation of mouse RECK gene is the Sp1 site, where the Sp1 and Sp3 factors bind. Sp1 transcription factor family is involved in the basal level of promoter activity of many genes, as well as in dynamic regulation of gene expression; in a majority of cases as a positive regulator, or, as exemplified by the oncogene-mediated suppression of RECK gene expression, as a negative transcription regulator. The molecular mechanisms of the downregulation of mouse RECK gene and other tumor suppressor genes are just beginning to be uncovered. Understanding the regulation of these genes may help to develop strategies to restore their expression in tumor cells and, hence, suppress the cells' malignant behavior.