Highly specific overexpression of the transcription factor SOX11 in human malignant gliomas.
Malignant glioma comprises the majority of primary human brain tumors with 16,800 new cases reported each year in the USA. Its prognosis remains dismal despite numerous attempts to improve conventional therapeutic modalities. Therefore, much effort is devoted to the exploration of alternative forms of treatment such as immunotherapy. The identification of potential target structures highly overexpressed in brain tumors is a crucial prerequisite for the activation of the immune defense against malignant glioma cells. By screening an expression database for genes highly expressed in glioblastoma multiforme (GBM), we identified the Pit-Oct-Unc (POU) cooperating transcription factor SOX11 that is known to be crucially involved in brain development. Analysis of the expression pattern of SOX11 in different normal adult and fetal tissues by multiple tissue dot blot and by a highly sensitive quantitative PCR assay confirmed the selective overexpression of SOX11 in fetal brain tissue. Examination of tissue specimens obtained from malignant gliomas and from normal brain by quantitative real-time PCR (Q-RT-PCR) revealed upregulation of SOX11 in almost all tumor samples (15/16) as compared to the pooled normal brain. Seventy-five percent of the tumor samples (12/16) showed a 5- to more than 600-fold overexpression. We conclude that, after downregulation of SOX11 in the adult brain, its expression is reactivated during tumorigenesis and that SOX11 therefore represents a promising novel molecular target for adjuvant therapy of malignant gliomas.
Weigle
Bernd
B
Institute of Immunology, Technical University of Dresden, 01307 Dresden, Germany. weigle@rcs.urz.tu-dresden.de
Ebner
Reinhard
R
Temme
Achim
A
Schwind
Sandra
S
Schmitz
Marc
M
Kiessling
Andrea
A
Rieger
Michael A
MA
Schackert
Gabriele
G
Schackert
Hans K
HK
Rieber
E Peter
EP
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D006609:High Mobility Group Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D020411:Oligonucleotide Array Sequence Analysis; D050809:POU Domain Factors; D055751:SOXC Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D050809:POU Domain Factors; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors; D014157:Transcription Factors