Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells

BMC Cancer

Research Article

Silje AU Lauvrak¹  Ola Myklebost²  Jørn Henriksen²  Marianne Stabell²  Leonardo A Meza-Zepeda²  Moustapha Kassem³ 

[1] CAST, Cancer Stem Cell Innovation Centre, Department of Tumor Biology, The Norwegian Radium Hospital, Oslo University Hospital, N-0027, Oslo, Norway;CAST, Cancer Stem Cell Innovation Centre, Department of Tumor Biology, The Norwegian Radium Hospital, Oslo University Hospital, N-0027, Oslo, Norway;Department of Molecular Bioscience, University of Oslo, Oslo, Norway;Department of Endocrinology, University Hospital of Odense, Denmark & Stem Cell Unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia;

关键词: Zinc Finger Gene;    HMGA2 Protein;    Krab Domain;    Adipocytic Differentiation;    eGFP Fusion Protein;   

DOI  :  10.1186/1471-2407-10-329

 received in 2010-01-15, accepted in 2010-06-25,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe HMGA2 gene, coding for an architectural transcription factor involved in mesenchymal embryogenesis, is frequently deranged by translocation and/or amplification in mesenchymal tumours, generally leading to over-expression of shortened transcripts and a truncated protein.MethodsTo identify pathways that are affected by sarcoma-associated variants of HMGA2, we have over-expressed wild type and truncated HMGA2 protein in an immortalized mesenchymal stem-like cell (MSC) line, and investigated the localisation of these proteins and their effects on differentiation and gene expression patterns.ResultsOver-expression of both transgenes blocked adipogenic differentiation of these cells, and microarray analysis revealed clear changes in gene expression patterns, more pronounced for the truncated protein. Most of the genes that showed altered expression in the HMGA2-overexpressing cells fell into the group of NF-κB-target genes, suggesting a central role for HMGA2 in this pathway. Of particular interest was the pronounced up-regulation of SSX1, already implicated in mesenchymal oncogenesis and stem cell functions, only in cells expressing the truncated protein. Furthermore, over-expression of both HMGA2 forms was associated with a strong repression of the epithelial marker CD24, consistent with the reported low level of CD24 in cancer stem cells.ConclusionsWe conclude that the c-terminal part of HMGA2 has important functions at least in mesenchymal cells, and the changes in gene expression resulting from overexpressing a protein lacking this domain may add to the malignant potential of sarcomas.

【 授权许可】

Unknown   
© Henriksen et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.