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A novel MASH1 enhancer with N-myc and CREB-binding sites is active in neuroblastoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2007 (English)In: Cancer Gene Therapy, ISSN 0929-1903, E-ISSN 1476-5500, Vol. 14, no 3, 287-296 p.Article in journal (Refereed) Published
Abstract [en]

Neuroblastoma is one of the most common solid tumors in childhood. With the aim of developing a targeting vector for neuroblastoma, we cloned and characterized an enhancer in the 5'-flanking regions of the MASH1 gene by a random-trap method from a 36 kb cosmid DNA. The enhancer-containing clone was identified by the expression of GFP when transfected into neuroblastoma cell lines. The enhancer-luciferase activity is higher in neuroblastoma cell lines, IMR32, BE2 and SH-SY5Y, compared with those in non-neuroblastoma cell lines, U1242 glioma, N417 small cell lung cancer and EOMA hemangioma. The core enhancer was determined within a 0.2 kb fragment, yielding three- to fourfold higher activity than that of the MASH1 promoter alone in IMR32 and BE2. This area possesses GATA- and CREB-binding sites, as well as the E-box. EMSA on this area demonstrated that CREB/ATF could bind the DNA. Chromatin immunoprecipitation assay revealed that N-myc, CREB, and co-activators CBP and PCAF, but not HDAC1, are bound to the core enhancer at the same time as the co-activators and N-myc bind to the promoter. This supports the idea that the commonly overexpressed genes HASH1 and N-myc are regulated in concert, confirming their importance as prognostic markers or targets for therapy.

Place, publisher, year, edition, pages
2007. Vol. 14, no 3, 287-296 p.
Keyword [en]
MASH1, HASH1, N-myc, CREB, enhancer, neuroblastoma
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-146026DOI: 10.1038/sj.cgt.7701012ISI: 000244207600008PubMedID: 17124508OAI: oai:DiVA.org:uu-146026DiVA: diva2:397430
Available from: 2011-02-14 Created: 2011-02-14 Last updated: 2011-02-14Bibliographically approved

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