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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2012.tde-24052012-085615
Document
Author
Full name
Dayson Friaça Moreira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Belizario, Jose Ernesto (President)
Camillo, Cláudia Malheiros Coutinho
Colquhoun, Alison
Rodrigues, Elaine Guadelupe
Santelli, Glaucia Maria Machado
Title in Portuguese
Avaliação da expressão dos genes envolvidos na via de sinalização induzida pela proteína dermicidina no câncer de mama.
Keywords in Portuguese
Células cultivadas de tumor
Dermicidina
Expressão gênica
Neoplasias mamárias
Proliferação celular
Sobrevivência celular
Abstract in Portuguese
A expressão do gene Dermicidina (DCD) no câncer de mama promove aumento na proliferação e sobrevivência celular, porém os mecanismos envolvidos são desconhecidos. Através de um ensaio de microarranjos de DNA demonstramos que o DCD desempenha atividade de fator de crescimento pela modulação da via de sinalização EGF/ErbB. Estes dados foram confirmados através de silenciamento gênico, superexpressão e tratamento com a proteína recombinante. O silenciamento diminuiu a expressão de EGFR e seus ligantes, e reduziu a ativação da via de sinalização EGF/ErbB. O tratamento da linhagem celular MDA-MB-361 com DCD recombinante resultou em uma curva de proliferação em forma de sino com concomitante aumentou a expressão de EGFR e seus ligantes. A superexpressão de DCD na linhagem MCF-7 também resultou no aumento da expressão dos receptores EGFR e HER-2 e de seus ligantes, além da ativação de suas vias de sinalização. Este trabalho sugere que o DCD é capaz de modular a expressão e ativação da família EGF/ErbB resultando no aumento do crescimento e sobrevivência celular.
Title in English
Evaluation of the expression of genes involved in signaling pathway induced by the protein dermicidin in breast cancer.
Keywords in English
Breast neoplasms
Cell proliferation
Cell survival
Cultured tumor cells
Dermicidina
Gene expression
Abstract in English
The expression of the gene Dermicidin (DCD) in breast cancer promotes increased in cell growth and survival, however the mechanisms involved are unknown. Using a DNA microarray assay we demonstrated that the DCD activity plays by modulating growth factor signaling phathway of EGF/ErbB. These data were confirmed by gene silencing, overexpression and treatment with the recombinant protein. The silencing decreased the expression of EGFR and its ligands, and reduced the activation of the EGF/ErbB signaling pathways. The treatment of MDA-MB-361 cell line with recombinant DCD resulted in a proliferation curve bell-shaped with a concomitant increased in the expression of the EGFR and its ligands. The overexpression of the DCD in the MCF-7 cell line also resulted in increased expression of the receptors HER-2 and EGFR and its ligands, and activation of theirs signaling pathways. This work suggests that DCD is able to modulate the expression and activation of the EGF/ErbB family resulting in increased of cellular growth and survival.
 
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Publishing Date
2012-06-04
 
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