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Master's Dissertation
DOI
10.11606/D.87.2012.tde-05022013-083629
Document
Author
Full name
Hátylas Felype Zaneti de Azevedo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Moreira Filho, Carlos Alberto (President)
Colquhoun, Alison
Santelli, Glaucia Maria Machado
Title in Portuguese
Sinalização mediada pela angiotensina II em um modelo de glioblastoma multiforme: uso da genômica funcional na identificação do papel dos receptores AT1 e AT2.
Keywords in Portuguese
Angiotensina II
Bioinformática
Biologia molecular
Biotecnologia
Genômica
Oncologia
Abstract in Portuguese
A expressão dos receptores AT1 e AT2 da Angiotensina II (Ang II) em astrocitomas humanos está associada a um pior prognóstico. Para investigar os mecanismos moleculares da ação da Ang II em gliomas, foi analisado por DNA microarray o transcriptoma da linhagem celular C6 tratada com Ang II e antagonistas de AT1 e AT2 nos intervalos de 3 e 6 horas. Os genes diferencialmente expressos obtidos foram submetidos a análises de enriquecimento funcional, diagramas de Venn e interatomas. As alterações observadas no transcriptoma a partir do tratamento com Ang II revelaram genes envolvidos em funções biológicas e vias de sinalização pró-tumorais tais como ciclo celular, migração, ErbB, MAPK e mTOR. Além disso, a identificação das proteínas centrais nos interatomas avaliados forneceu evidências para estudos futuros com foco nesses alvos. Embora a transdução de sinal de AT2 seja distinta da observada em AT1, ambas apresentaram categorias funcionais em comum que podem estar relacionadas ao pior prognóstico observado em pacientes cujos gliomas expressam esses receptores.
Title in English
Transcriptome profile regulated by Angiotensin II in glioma cells: potential insights into the role of AT1 and AT2 receptors.
Keywords in English
Angiotensin II
Bioinformatics
Biotechnology
Genomics
Molecular biology
Oncology
Abstract in English
The expression of AT1 and AT2 receptors of Angiotensin II (Ang II) in human astrocytomas was associated with a worse prognosis. To investigate the molecular mechanisms of Ang II actions in gliomas, the transcriptomic profile of C6 cells treated with Ang II and antagonists of AT1 and AT2 was evaluated. The differentially expressed genes obtained were submitted to functional enrichment, Venn diagram and transcriptome network analyzes. Ang II treatment caused gene expression changes involved in pro-tumor functions and signaling pathways such as cell cycle, migration, ErbB, mTOR and MAPK. Furthermore, the identification of central proteins in the interactomes provided evidences for future studies focused on these targets. Taken together, these results provided insights into how the transcriptome of glioma cells is affected by Ang II. Moreover, although the signal transduction of AT2 is distinct from the observed for AT1, they present functional categories in common that may be underlying the worst prognosis observed in gliomas expressing Ang II receptors.
 
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Publishing Date
2013-02-22
 
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