HIF-1alpha induces MXI1 by alternate promoter usage in human neuroblastoma cells.

Summary, in English

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 a long-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.

• Författare: Tobias Löfstedt; Erik Fredlund; Rosa Noguera; Samuel Navarro; Linda Holmquist Mengelbier; Siv Beckman; Sven Påhlman; Håkan Axelson
• Avdelning/ar: Institutionen för translationell medicin
• Publiceringsår: 2009
• Språk: Engelska
• Sidor: 1924-1936
• Publikation/Tidskrift/Serie: Experimental Cell Research
• Volym: 315
• Issue: 11
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/19254710?dopt=Abstract; http://dx.doi.org/10.1016/j.yexcr.2009.02.015
• Dokumenttyp: Artikel i tidskrift
• Förlag: Academic Press
• Ämne: Cancer and Oncology
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1090-2422