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Knock-down of SOX11 induces autotaxin-dependent increase in proliferation in vitro and more aggressive tumors in vivo

Conrotto, Paolo LU ; Andreasson, Ulrika LU ; Kuci, Venera LU ; Borrebaeck, Carl LU and Ek, Sara LU (2011) In Molecular Oncology 5. p.527-537
Abstract (Swedish)
Abstract in Undetermined

The transcription factor SOX11 is a novel diagnostic marker for mantle cell lymphoma (MCL), distinguishing this aggressive tumor from potential simulators. Recent data also show that the level of SOX11 correlates to in vitro growth properties in MCL, as well as the clinical progression. We have previously shown that MCL-associated pathways, such as Rb-E2F, are dysregulated leading to decreased proliferation upon overexpression of SOX11, emphasizing the impact of SOX11 on MCL-specific gene expression and growth control. However, it remains to be determined which growth regulatory pathways that are induced upon SOX11 knock-down, leading to an increased cellular growth. Consequently, we established a... (More)
Abstract in Undetermined

The transcription factor SOX11 is a novel diagnostic marker for mantle cell lymphoma (MCL), distinguishing this aggressive tumor from potential simulators. Recent data also show that the level of SOX11 correlates to in vitro growth properties in MCL, as well as the clinical progression. We have previously shown that MCL-associated pathways, such as Rb-E2F, are dysregulated leading to decreased proliferation upon overexpression of SOX11, emphasizing the impact of SOX11 on MCL-specific gene expression and growth control. However, it remains to be determined which growth regulatory pathways that are induced upon SOX11 knock-down, leading to an increased cellular growth. Consequently, we established a model cell line with constitutive down-regulation of SOX11. The highly proliferative features of this cell line were investigated by gene expression analysis, proliferation assay, cell cycle distribution and potential to induce tumors in NOD-SCID mice. Our in vitro studies demonstrated a SOX11-dependent regulation of MCL-specific gene expression. In addition, we identified autotaxin (ATX) to be regulated by SOX11. Our results clearly showed a correlation between SOX11 level and cellular growth rate, which was dependent on ATX, as well as a direct relation between the level of SOX11 in tumorigenic cells and the growth rate of these tumors in NOD-SCID mice. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Oncology
volume
5
pages
527 - 537
publisher
Elsevier
external identifiers
  • wos:000298205100005
  • pmid:21880559
  • scopus:80053575683
ISSN
1574-7891
DOI
10.1016/j.molonc.2011.08.001
language
English
LU publication?
yes
id
6a49faa6-2d42-496a-afb2-536aabe034cc (old id 2064195)
date added to LUP
2011-08-18 13:54:57
date last changed
2017-01-01 03:02:03
@article{6a49faa6-2d42-496a-afb2-536aabe034cc,
  abstract     = {<b>Abstract in Undetermined</b><br/><br>
The transcription factor SOX11 is a novel diagnostic marker for mantle cell lymphoma (MCL), distinguishing this aggressive tumor from potential simulators. Recent data also show that the level of SOX11 correlates to in vitro growth properties in MCL, as well as the clinical progression. We have previously shown that MCL-associated pathways, such as Rb-E2F, are dysregulated leading to decreased proliferation upon overexpression of SOX11, emphasizing the impact of SOX11 on MCL-specific gene expression and growth control. However, it remains to be determined which growth regulatory pathways that are induced upon SOX11 knock-down, leading to an increased cellular growth. Consequently, we established a model cell line with constitutive down-regulation of SOX11. The highly proliferative features of this cell line were investigated by gene expression analysis, proliferation assay, cell cycle distribution and potential to induce tumors in NOD-SCID mice. Our in vitro studies demonstrated a SOX11-dependent regulation of MCL-specific gene expression. In addition, we identified autotaxin (ATX) to be regulated by SOX11. Our results clearly showed a correlation between SOX11 level and cellular growth rate, which was dependent on ATX, as well as a direct relation between the level of SOX11 in tumorigenic cells and the growth rate of these tumors in NOD-SCID mice.},
  author       = {Conrotto, Paolo and Andreasson, Ulrika and Kuci, Venera and Borrebaeck, Carl and Ek, Sara},
  issn         = {1574-7891},
  language     = {eng},
  pages        = {527--537},
  publisher    = {Elsevier},
  series       = {Molecular Oncology},
  title        = {Knock-down of SOX11 induces autotaxin-dependent increase in proliferation in vitro and more aggressive tumors in vivo},
  url          = {http://dx.doi.org/10.1016/j.molonc.2011.08.001},
  volume       = {5},
  year         = {2011},
}