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Previous issue date: 2015-05-29 / Background ? Recent studies have demonstrated that the chromatin structure proteins named histones have an important role in gene expression. Acetylation, deacetylation and fosforylation of such proteins may result in upregulation or repression of transcription genes. An imbalance of these systems may result in the development of many diseases, including cancer. Sirtuin 1 (SIRT1) is a member of the family of histone deacetylases NAD ? dependents and is involved in the regulation of transcription and apoptosis activation related to p53 gene. There are several changes in the expression of hormone receptors and p53 in endometrial cancer, but the role of SIRT1 in these tumors is still to be defined. Objective - To identify, quantify and compare SIRT1, p53, estrogen receptor (ER) and progesterone receptor (PR) expression in normal and neoplastic endometrial tissue. Methods ? Case-control study comparing 96 cases of endometrial cancer and 128 control samples comprised of normal endometrium. All samples were selected from the Pathology Service, Hospital Sao Lucas of PUCRS between January, 2000 and June, 2012. The factors studied in this paper were analyzed in paraffin specimens by immunohistochemistry technique. Results ? Expression of SIRT1 was assessed by the mean percentage of cells with positive nuclear staining was higher in the cancer group as compared to the control group. Expression of ER and PR was higher in the normal endometrium. There is no difference between case and control groups regarding the expression of p53. More aggressive cancers (high grade and stage III-IV) have a reduction on the expression of PR. Conclusion ? The immunohistochemical expression of SIRT1 histone deacetylase was significantly higher in endometrial cancer samples, suggesting a possible new target therapy. / Introdu??o ? Estudos recentes t?m demonstrado que as histonas, prote?nas da estrutura da cromatina, exercem um papel importante na express?o g?nica. Modifica??es como acetila??o, desacetila??o e fosforila??o de histonas podem resultar em um aumento ou repress?o de genes de transcri??o. Um desbalan?o nestes sistemas pode levar ao desenvolvimento de diversas doen?as, incluindo c?ncer. A Sirtuina 1 (SIRT1) pertence a fam?lia de histonas desacetilases NAD ? dependentes e est? envolvida com a regula??o da ativa??o da transcri??o e apoptose relacionada ao gene p53 (gene supressor tumoral). H? v?rias altera??es na express?o de receptores hormonais e p53 em c?ncer de endom?trio, mas o papel de SIRT1 nestes tumores ainda est? para ser definido. Objetivos - Identificar, quantificar e comparar a express?o da enzima SIRT1, p53 e receptores hormonais de estrog?nio (RE) e progesterona (RP) em amostras de endom?trio tumoral e normal.Popula??o e M?todos ? Estudo de caso-controle comparando 96 casos de c?ncer de endom?trio e 128 controles (endom?trio sadio) a partir de amostras do banco de dados do Setor de Patologia do Hospital S?o Lucas da PUCRS no per?odo de janeiro de 2000 a junho de 2012. Os esp?cimes em parafina foram submetidos ? pesquisa dos fatores em estudo atrav?s da t?cnica de imunohistoqu?mica. Resultados ? A express?o de SIRT1 avaliada pelo percentual m?dio de positividade nuclear de c?lulas foi significativamente maior nos tumores em compara??o com os controles, ao passo que a express?o de RE e RP foi maior no endom?trio sadio. N?o houve diferen?a na express?o de p53 entre casos e controles. Os tumores mais agressivos (maior grau e estadiamento III-IV) tiveram redu??o significativa na express?o de RP. Conclus?o ? A express?o de SIRT1 foi maior nos tumores de endom?trio, sugerindo um poss?vel alvo terap?utico.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/6243 |
| Date | 29 May 2015 |
| Creators | Marc, Chrystiane da Silva |
| Contributors | Silva, Vinicius Duval da |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de, PUCRS, Brasil, Faculdade de Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7620745074616285884, 600, 600, 600, -8624664729441623247, -969369452308786627 |
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