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prando_ec_dr_botib.pdf: 1650912 bytes, checksum: 61a3213e2810a3629780bb8a28aa87c8 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Atualmente, o silenciamento de genes supressores de tumor por mecanismos epigenéticos é reconhecido como uma característica importante das células tumorais. Estudos recentes mostraram que as alterações da metilação do DNA não estão restritas a genes discretos, mas podem afetar ilhas CpG consecutivas em algumas regiões genômicas, levando à hipótese de que mecanismos epigenéticos coordenados poderiam silenciar simultaneamente a expressão de vários genes. A perda da expressão da isoforma A do gene RASSF1, localizado em 3p21.3 (uma região cromossômica frequentemente deletada no câncer), constitui um dos principais exemplos de genes que são inativados tanto por mecanismos genéticos quanto epigenéticos no câncer, incluindo os carcinomas mamários. Este estudo teve como finalidade investigar a ocorrência de alterações epigenéticas em um agrupamento gênico em 3p21.3 contendo vários genes candidatos a supressores tumorais. Foram selecionados 10 genes contíguos (SEMA3B, HYAL3, HYAL1, HYAL2 TUSC2, RASSF1, ZMYND10, NPRL2, TMEM115 e CACNA2D2) e um painel de 17 linhagens celulares derivadas de carcinomas mamários (BT-20, BT-474, BT-483, BT-549, Hs578T, MCF7, MDA-MB-134 IV, MDA-MB-231, MDA-MB-361, MDA-MB-415, MDA-MB-436, MDAMB- 453, MDA-MB-468, SK-BR-3, T-47D, ZR-75-1 e ZR-75-30), uma linhagem epitelial derivada de doença fibrocística benigna da mama (MCF10A) e duas linhagens derivadas de epitélio mamário normal (184A1 e 184B5). Inicialmente, os níveis de expressão foram quantificados por qRT-PCR (quantitative real time Reverse Transcriptase-Polymerase Chain Reaction) após o tratamento das linhagens com as drogas 5-aza-2’-desoxicitidina (5AzadC), um agente desmetilante, e tricostatina A (TSA), um inibidor das desacetilases de histonas em... / Currently, the silencing of tumor suppressor genes by epigenetic mechanisms is recognized as an important feature of tumor cells. Recent studies have showed that aberrant DNA methylation patterns are not restricted to discrete genes, but also could affect consecutive CpG islands in some genomic regions, which suggested that epigenetically coordinated mechanisms could lead to the simultaneous silencing of cancer-related genes. The loss of expression of the isoform A of the RASSF1 gene, mapped at 3p21.3 (a chromosomal region frequently deleted in cancer), is listed among those genes inactivated by both, genetic and epigenetic mechanisms in human cancer, including breast carcinomas. The purpose of this study was to investigate the occurrence of epigenetic alterations in a gene cluster at 3p21.3 which contains several candidates to tumor suppressor genes. It was selected 10 contiguous genes (SEMA3B, HYAL3, HYAL1, HYAL2 TUSC2, RASSF1, ZMYND10A, NPRL2, TMEM115 and CACNA2D2) and a panel of 17 breast cancer cell lines (BT-20, BT-474, BT- 483, BT-549, Hs578T, MCF7, MDA-MB-134 IV, MDA-MB-231, MDA-MB-361, MDA-MB-415, MDA-MB-436, MDA-MB-453, MDA-MB-468, SK-BR-3, T-47D, ZR-75-1 and ZR-75-30), one cell line derived from benign fibrocystic disease of the breast (MCF10A) and two cell lines derived from normal mammary epithelium (184A1 and 184B5). Initially, the expression levels were quantified by qRT-PCR (quantitative real time Reverse Transcriptase-Polymerase Chain Reaction) after the treatments of the cell lines with the 5-aza-2'-deoxycytidine (5Azadc), a DNA demethylating agent and trichostatin A (TSA) a histone deacetylase inhibitor, relative to the untreated controls. The results obtained showed that RASSF1 transcripts were detected in all cell lines; however, the expression of RASSF1A isoform was detected only in the Hs578T and... (Complete abstract click electronic access below)
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.unesp.br:11449/102684 |
| Date | 01 June 2011 |
| Creators | Prando, Érika da Costa [UNESP] |
| Contributors | Universidade Estadual Paulista (UNESP), Rainho, Cláudia Aparecida [UNESP] |
| Publisher | Universidade Estadual Paulista (UNESP) |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | Portuguese |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | 87 f. |
| Source | Aleph, reponame:Repositório Institucional da UNESP, instname:Universidade Estadual Paulista, instacron:UNESP |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | -1, -1 |
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