SOX11 expression correlates to promoter methylation and regulates tumor growth in hematopoietic malignancies

Molecular Cancer

Research

Elin Andersson¹  Sara Ek²  Carl A. K. Borrebaeck²  Elin Gustavsson²  Sandra Sernbo²  Mats Jerkeman³  Michael Dictor⁴  Donal J. Brennan⁵ 

[1] Department of Immunotechnology, Lund University, Lund, Sweden;Department of Immunotechnology, Lund University, Lund, Sweden;CREATE Health, Lund University, BMC D13, 221 84, Lund, Sweden;Department of Oncology, Lund University Hospital, Lund, Sweden;Department of Pathology, Lund University Hospital, Lund, Sweden;UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland;

关键词: Follicular Lymphoma;    Mantle Cell Lymphoma;    SOX11 Expression;    SOX11 Protein;    SOX11 mRNA;   

DOI  :  10.1186/1476-4598-9-187

 received in 2010-04-12, accepted in 2010-07-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe transcription factor SOX11 plays an important role in embryonic development of the central nervous system (CNS) and is expressed in the adult immature neuron but is normally not expressed in any other adult tissue. It has recently been reported to be implicated in various malignant neoplasms, including several lymphoproliferative diseases, by its specific expression and in some cases correlation to prognosis. SOX11 has been shown to prevent gliomagenesis in vivo but the causes and consequences of aberrant expression of SOX11 outside the CNS remain unexplained.ResultsWe now show the first function of SOX11 in lymphoproliferative diseases, by demonstrating in vitro its direct involvement in growth regulation, as assessed by siRNA-mediated silencing and ectopic overexpression in hematopoietic malignancies. Gene Chip analysis identified cell cycle regulatory pathways, including Rb-E2F, to be associated with SOX11-induced growth reduction. Furthermore, promoter analysis revealed that SOX11 is silenced through DNA methylation in B cell lymphomas, suggesting that its regulation is epigenetically controlled.ConclusionsThe data show that SOX11 is not a bystander but an active and central regulator of cellular growth, as both siRNA-mediated knock-down and ectopic overexpression of SOX11 resulted in altered proliferation. Thus, these data demonstrate a tumor suppressor function for SOX11 in hematopoietic malignancies and revealed a potential epigenetic regulation of this developmentally involved gene.

【 授权许可】

Unknown   
© Gustavsson 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.