期刊
EXPERIMENTAL CELL RESEARCH
卷 315, 期 11, 页码 1924-1936出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2009.02.015
关键词
MXI1; Hypoxia; HIF-1; Hypoxia responsive elements (HRE); Neuroblastoma; MYCN
资金
- Swedish Cancer Society
- Children's Cancer Foundation of Sweden
- Swedish Research Council
- Swedish Foundation
- Swedish Knowledge Foundation
- Ollie and Elof Ericsson's
- Crafoord's
- Hans von Kantzow's and Gunnar Nilsson's foundations
- Malmo University Hospital
- Instituto Carlos III, Madrid, Spain [RD06/0020/0102, P106/1576]
Adaptation to low oxygen conditions is essential for maintaining homeostasis and viability in oxygen-consuming multi-cellular tissues, including solid tumors. Central in these processes are the hypoxia-inducible transcription factors, HIF-1 and HIF-2, controlling genes involved in e.g. glucose metabolism and neovascularization. Tumor hypoxia and HIF expression have also been associated with a dedifferentiated phenotype and increased aggressiveness. In this report we show that the MAX interactor-1 (MXI1) gene is directly regulated by HIF proteins in neuroblastoma and breast cancer cells. HIF-binding and transactivation were detected within MXI1 gene regulatory sequences in the vicinity of the MXI1-0 promoter, leading to rapid induction of the alternate MXI1-0 isoform followed by along-term induction of both the MXI1-0 and MXI1 isoforms. Importantly, knock-down of MXI1 had limited effect on MYC/MYCN activity under hypoxia, an observation that might be related to the different functional attributes of the two MXI1 isoforms. (C) 2009 Elsevier Inc. All rights reserved.
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