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


RESULTS
We 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.


CONCLUSIONS
The 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.
Gustavsson
Elin
E
Department of Immunotechnology, Lund University, Lund, Sweden.
Sernbo
Sandra
S
Andersson
Elin
E
Brennan
Donal J
DJ
Dictor
Michael
M
Jerkeman
Mats
M
Borrebaeck
Carl Ak
CA
Ek
Sara
S
D002455:Cell Division; D019175:DNA Methylation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D011401:Promoter Regions, Genetic; D055751:SOXC Transcription Factors / Q000235:genetics*
C097473:SOX11 protein, human; D055751:SOXC Transcription Factors