BCR/ABL induces faim overexpression, a potential new target for therapy (2006)
- USP affiliated authors: MOREIRA FILHO, CARLOS ALBERTO - ICB ; CASTRO, FABÍOLA ATTIÉ DE - FCFRP
- Unidades: ICB; FCFRP
- Assunto: IMUNOLOGIA
- Language: Inglês
- Abstract: Introduction and Objectives : Chronic myelogenous leukemia (CML) is a stem cell disease characterized by the presence of the Bcr-Abl oncoprotein, which is the cause of the malignant transformation and the extreme resistance to apoptosis displayed by CML patients. A significant effort is being made to elucidate the alterations in gene expression, in particular genes involved in apoptosis, cell cycle, metabolism and signaling transduction. Hence, our aim was to analyze the alteration in global gene expression in cells that were ectopically transfected with Bcr-Abl or with an empty vector. Subsequently, we plan to evaluate the potential of some of the modified genes as therapeutic targets or prognostic markers for CML. Methods and Results: Ectopic expression of Bcr-Abl in HL-60, HeLa and SKW6.4 cells was previously established by our group. Apoptosis was evaluated against different stimuli by detecting annexin V-binding and DNA content. Bcr-Abl expression conferred resistance to death in HL-60 and HeLa, but not in SKW6.4 cells. Global gene expression of wild-type and Bcr-Abl-positive cells was evaluated by microarray.We identified 465 genes overexpressed and 70 underexpressed in cells resistant to apoptosis. These genes are mainly related to cell motility, communication, growth, signal transduction, metabolism and cell death. One of the overexpressed genes was the Fas Apoptosis Inhibitory Molecule (faim), which showed significant upregulation(13,5 times higher in HL60.Bcr-Abl than in HL60). These results were further confirmed by Real-Time PCR. As faim was described as an antagonist of the Fas pathway and one of the mechanisms responsible for anti-cancer activity of the immune cells is the killing of tumor cells by the Fas/FasL interaction, the study of this antiapoptotic protein may identify a promising target for new therapy in CML. Conclusion : Ectopic expression of Bcr-Abl protects HL-60 and HeLa, but not SKW6.4 from apoptosis, suggesting that cellular context is important to Bcr-Abl cell malignant transformation and apoptosis resistance. The differentially expressed gene faim deserves further investigation to evaluate its correlation with CML.
- Título do periódico: Abstracts
- Conference titles: Meeting of the Brazilian Society for Immunology
ABNTLEROY, J M G; CARVALHO, D D; PEREIRA, W O; et al. BCR/ABL induces faim overexpression, a potential new target for therapy. Anais.. São Paulo: [s.n.], 2006.
APALeroy, J. M. G., Carvalho, D. D., Pereira, W. O., Bueno-da-Silva, A. E., Jacysyn, J. F., Lopes, L. R., et al. (2006). BCR/ABL induces faim overexpression, a potential new target for therapy. In Abstracts. São Paulo.
NLMLeroy JMG, Carvalho DD, Pereira WO, Bueno-da-Silva AE, Jacysyn JF, Lopes LR, Vencio RZ, Tobo PR, Okamoto OK, Moreira-Filho CA, Castro FA de. BCR/ABL induces faim overexpression, a potential new target for therapy. Abstracts. 2006 ;
VancouverLeroy JMG, Carvalho DD, Pereira WO, Bueno-da-Silva AE, Jacysyn JF, Lopes LR, Vencio RZ, Tobo PR, Okamoto OK, Moreira-Filho CA, Castro FA de. BCR/ABL induces faim overexpression, a potential new target for therapy. Abstracts. 2006 ;
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