Continuous Fli-1 expression plays an essential role in the proliferation and survival of F-MuLV-induced erythroleukemia and human erythroleukemia
| Autor: | Cui Jw, Guan Wang, Ben-David Y, You-Jun Li, Vecchiarelli-Federico Lm |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Cell Survival Cellular differentiation Down-Regulation Biology Proto-Oncogene Mas Mice Downregulation and upregulation RNA interference hemic and lymphatic diseases Cell Line Tumor medicine Gene silencing Animals Humans Cell Proliferation DNA Primers Base Sequence Cell growth Proto-Oncogene Protein c-fli-1 Reverse Transcriptase Polymerase Chain Reaction fungi Cell Differentiation Hematology medicine.disease Immunohistochemistry Leukemia Virus Murine Leukemia Oncology Apoptosis Cell culture Cancer research RNA Interference Leukemia Erythroblastic Acute |
| Zdroj: | Leukemia. 23(7) |
| ISSN: | 1476-5551 |
| Popis: | Erythroleukemia induced by Friend Murine Leukemia Virus (F-MuLV) serves as a powerful tool for the study of multistage carcinogenesis and hematological malignancies in mice. Fli-1, a proto-oncogene and member of the Ets family, is activated through viral integration in F-MuLV-induced erythroleukemia, and is the most critical event in the induction of this disease. Fli-1 aberrant regulation is also observed in human malignancies, including Ewing's sarcoma, which is often linked to expression of the EWS/Fli-1 fusion oncoprotein. Here we examined the effects of Fli-1 inhibition to further elucidate its role in these pathological occurrences. The constitutive suppression of Fli-1, through RNA interference (RNAi), inhibits growth and induces death in F-MuLV-induced erythroleukemia cells. Expression of a dominant negative protein Engrailed (En)/Fli-1 reduces proliferation of EWS/Fli-1-transformed NIH-3T3 cells, and both F-MuLV-induced and human erythroleukemia cells. F-MuLV-induced erythroleukemia cells also display increased apoptosis, associated with reduced expression of bcl-2, a known fli-1 target gene. Introduction of En/Fli-1 into an F-MuLV-infected erythroblastic cell line induces differentiation, as shown by increased alpha-globin expression. These results suggest, for the first time, an essential role for continuous Fli-1 overexpression in the maintenance and survival of the malignant phenotype in murine and human erythroleukemias. |
| Databáze: | OpenAIRE |
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