Hypoxia-inducible factor-1 alpha-induced differentiation of myeloid leukemic cells is its transcriptional activity independent
文献类型:期刊论文
作者 | Song, L-P1,2; Zhang, J.1,2; Wu, S-F1,2; Huang, Y.3; Zhao, Q.1,2; Cao, J-P1,2; Wu, Y-L3; Wang, L-S3; Chen, G-Q1,2,3 |
刊名 | Oncogene
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出版日期 | 2008-01-17 |
卷号 | 27期号:4页码:519-527 |
关键词 | Leukemia Differentiation Hif-1 alpha C/ebp alpha |
ISSN号 | 0950-9232 |
DOI | 10.1038/sj.onc.1210670 |
通讯作者 | Chen, g-q(chengq@shsmu.edu.cn) |
英文摘要 | Hypoxia or hypoxia mimetic has been shown to induce differentiation together with the accumulation of hypoxia-inducible factor-1 alpha (hif-1 alpha) protein of myeloid leukemic cells and normal hematopoietic progenitors. to provide direct evidence for the role of hif-1 alpha in acute myeloid leukemia (aml) cell differentiation and its mechanisms, we generated myeloid leukemic u937t transformants, in which hif-1 alpha was tightly induced by tetracycline withdrawal. the results showed that the conditional hif-1 alpha induction triggered granulocytic differentiation of these transformants, while the suppression of hif-1 alpha expression by specific short hairpin rnas (shrnas) effectively inhibited hypoxia-induced differentiation of u937 cells, as evidenced by morphology, maturation-related antigens as well as expressions of myeloid differentiation signatures and hematopoietic cells- specific cytokine receptors. the specific shrnas-inhibited expression of hif-1 beta, an essential partner for transcription activity of hif-1 alpha failed, while the inhibition of hematopoietic differentiation-critical ccaat/enhancer-binding protein-a (c/ebpa) significantly eliminated hif-1 alpha-mediated myeloid leukemic cell differentiation. collectively, this work provided several lines of direct evidence for the role of hif-1 alpha protein through its nontranscriptional activity in myeloid cell differentiation, in which c/ebp alpha elicitsa role as an effector downstream to hif-1 alpha. these discoveries would shed new insights for understanding mechanisms underlying leukemogenesis and designing the new therapeutic strategy for differentiation induction of aml. |
WOS关键词 | PHOSPHOLIPID SCRAMBLASE-1 GENE ; TEL-ARNT FUSION ; OXYGEN-TENSION ; RETINOIC ACID ; C/EBP-ALPHA ; EXPRESSION ; ARREST ; TRANSLOCATION |
WOS研究方向 | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
WOS类目 | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
语种 | 英语 |
WOS记录号 | WOS:000252426100012 |
出版者 | NATURE PUBLISHING GROUP |
URI标识 | http://www.irgrid.ac.cn/handle/1471x/2389910 |
专题 | 中国科学院大学 |
通讯作者 | Chen, G-Q |
作者单位 | 1.SJTU SM, Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China 2.SJTU SM, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China 3.SJTU SM, Chinese Minist Educ, Key Lab Cell Differentiat & Apoptosis, Dept Pathophysiol, Shanghai, Peoples R China |
推荐引用方式 GB/T 7714 | Song, L-P,Zhang, J.,Wu, S-F,et al. Hypoxia-inducible factor-1 alpha-induced differentiation of myeloid leukemic cells is its transcriptional activity independent[J]. Oncogene,2008,27(4):519-527. |
APA | Song, L-P.,Zhang, J..,Wu, S-F.,Huang, Y..,Zhao, Q..,...&Chen, G-Q.(2008).Hypoxia-inducible factor-1 alpha-induced differentiation of myeloid leukemic cells is its transcriptional activity independent.Oncogene,27(4),519-527. |
MLA | Song, L-P,et al."Hypoxia-inducible factor-1 alpha-induced differentiation of myeloid leukemic cells is its transcriptional activity independent".Oncogene 27.4(2008):519-527. |
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来源:中国科学院大学
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