Department of Immunotechnology, Lund University, BMC D13, SE-221 84 Lund, Sweden.
Mol Oncol. 2011 Dec;5(6):527-37. doi: 10.1016/j.molonc.2011.08.001. Epub 2011 Aug 22.
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.
转录因子 SOX11 是套细胞淋巴瘤 (MCL) 的一种新型诊断标志物，可将这种侵袭性肿瘤与潜在的模拟物区分开来。最近的数据还表明，SOX11 的水平与 MCL 体外生长特性以及临床进展相关。我们之前已经表明，MCL 相关途径，如 Rb-E2F，失调导致 SOX11 过表达时增殖减少，强调了 SOX11 对 MCL 特异性基因表达和生长控制的影响。然而，仍然需要确定在 SOX11 敲低时诱导哪些生长调节途径，从而导致细胞生长增加。因此，我们建立了一种具有稳定下调 SOX11 的模型细胞系。通过基因表达分析、增殖测定、细胞周期分布和在 NOD-SCID 小鼠中诱导肿瘤的潜力来研究该细胞系的高度增殖特征。我们的体外研究表明 SOX11 依赖于 MCL 特异性基因表达的调节。此外，我们确定了自分泌运动因子 (ATX) 受 SOX11 调节。我们的结果清楚地显示了 SOX11 水平与细胞生长速率之间的相关性，该相关性依赖于 ATX，以及肿瘤发生细胞中 SOX11 水平与这些肿瘤在 NOD-SCID 小鼠中的生长速率之间的直接关系。
