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| Author(s): |
Daniel Diniz de Carvalho
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2009-11-23 |
| Examining board members: |
Joao Gustavo Pessini Amarante Mendes;
Eliana Saul Furquim Werneck Abdelhay;
Jose Alexandre Marzagao Barbuto;
Anamaria Aranha Camargo;
Mari Cleide Sogayar
|
| Advisor: | Joao Gustavo Pessini Amarante Mendes |
| Field of knowledge: | Biological Sciences - Immunology |
| Indexed in: | Banco de Dados Bibliográficos da USP-DEDALUS; Biblioteca Digital de Teses e Dissertações - USP |
| Location: | Universidade de São Paulo. Biblioteca do Instituto de Ciências Biomédicas; T-ICB BMI QW504; C331re |
| Abstract | |
TRAIL was shown to selectively kill tumor cells. Not surprisingly, TRAIL is down-regulated in a variety of tumor cells, but the mechanism responsible for TRAIL inhibition remains elusive. Because TRAIL can be regulate by retinoic acid; PRAME was shown to inhibit transcription of retinoic acid receptor target genes through the polycomb protein EZH2; and we have found that TRAIL is inversely correlated with BCR-ABL in CML patients, we decided to investigate the association of PRAME, EZH2 and TRAIL in BCR-ABL-positive leukemia. Here, we demonstrate that PRAME, but not EZH2, is up-regulated in BCR-ABL cells and is associated with the progression of disease in CML patients. In addition, PRAME expression is positively correlated with BCR-ABL and negatively with TRAIL in these patients. Importantly, knocking down of PRAME or EZH2 by RNA interference restores TRAIL expression. Our data reveal a novel regulatory mechanism responsible for lowering TRAIL expression and provide the basis of alternative targets for combined therapeutic strategies for CML. (AU) | |
| FAPESP's process: | 05/58764-0 - BCR-ABL-mediated regulation of SH3BGRL2, D53, PRAME, DAP12 and calcineurin A beta and biological consequences of this regulation on CML |
| Grantee: | Daniel Diniz de Carvalho |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |