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Doctoral Thesis
DOI
10.11606/T.42.2008.tde-03062008-153936
Document
Author
Full name
Ana Elisa Barreiros Bueno da Silva
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Mendes, Joao Gustavo Pessini Amarante (President)
Chammas, Roger
Hamerschlak, Nelson
Menck, Carlos Frederico Martins
Smaili, Soraya Soubhi
Title in Portuguese
Aspectos moleculares da transformação celular induzida por Bcr-Abl.
Keywords in Portuguese
Apoptose
Bcr-Abl
Leucemia mielóide crônica
Proteoma
Tirosina-quinase
Transformação celular
Abstract in Portuguese
As leucemias cromossomo Ph-positivas estão intimamente associadas à expressão da tirosina-quinase Bcr-Abl. Esta oncoproteína promove independência de fatores de crescimento, alterações na adesão e inibição da apoptose por mecanismos ainda não totalmente elucidados. O objetivo desse estudo foi avaliar a contribuição da atividade quinase de Bcr-Abl para seu potencial anti-apoptótico e identificar alterações moleculares envolvidas na transformação celular induzida por essa proteína. Nossos resultados sugerem que a resistência à apoptose não depende da manutenção constante da atividade tirosina-quinase de Bcr-Abl, tampouco da presença de proteínas fosforiladas em tirosina. A comparação do proteoma de células HL-60.vetor e HL-60.Bcr-Abl revelou que a presença de Bcr-Abl causa alterações profundas no padrão de expressão protéica. As proteínas afetadas estão associadas a diversos processos celulares, como adesão, transdução de sinais, proliferação e morte celular. Esses achados devem contribuir para a identificação de novos marcadores de prognóstico e alvos terapêuticos.
Title in English
Molecular aspects of Bcr-Abl-induced cell transformation.
Keywords in English
Apoptosis
Bcr-Abl
Cell transformation
Chronic myeloid leukemia
Proteome
Tyrosine kinase
Abstract in English
Ph chromosome-positive leukemias are closely associated with the expression of Bcr-Abl tyrosine kinase. This oncoprotein promotes growth factor independence, alters cell adhesion and confers resistance to apoptosis by mechanisms that are not fully understood. The aim of this study was to evaluate the contribution of Bcr-Abl kinase activity for its antiapoptotic potential and identify molecular alterations involved in Bcr-Abl-induced cell malignant transformation. Our results suggest that Bcr-Abl is not required to be constantly active to maintain the resistance to apoptosis and pY-containing proteins may not be responsible for the antiapoptotic effect of Bcr-Abl. The comparison between the proteome of HL-60.vector and HL-60.Bcr-Abl cells revealed that the presence of Bcr-Abl alters the expression of a great variety of proteins. The affected molecules are associated with several cellular processes, including cell adhesion, signal transduction, proliferation and cell death. Our findings might help the identification of new prognostic markers and therapeutic targets.
 
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Publishing Date
2008-06-11
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
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