Dr Senckenberg Institute of Neurooncology, Goethe-University Hospital Frankfurt, Frankfurt, Germany.
Int J Oncol. 2012 Jul;41(1):235-41. doi: 10.3892/ijo.2012.1446. Epub 2012 Apr 25.
PAX2 is a paired box transcription factor possessing a fundamental role in the embryogenesis of hindbrain and urinary tract. PAX genes are proto-oncogenes, PAX2 expression may contribute to the pathogenesis of renal cell carcinoma. Because of the expression of PAX2 in the developing hindbrain and its essential role in cerebellar development, it has been hypothesized that PAX2 may also be involved in medulloblastoma tumorigenesis. We investigated the expression pattern of PAX2 and various genes of the neuronal lineage in medulloblastoma and glioma cell lines. We found high expression of PAX2 mRNA and PAX2 protein in medulloblastoma cells and some glioma cell lines independent of their neuronal lineage gene expression signature. Gene suppression of PAX2 decreased the expression of the PAX2 transcriptional target GDNF in Daoy cells and had a profound cytotoxic effect in vitro on Daoy medulloblastoma and T98G glioma cells. Expression of PAX2 was then assessed in two separate medulloblastoma tissue microarrays with a total of 61 patient samples by immunohistochemistry. PAX2 expression was detected in the majority of medulloblastoma samples and correlated with less differentiated histology. Therefore, PAX2 is a biomarker for a more aggressive medulloblastoma phenotype and may represent a novel therapeutic target.
PAX2 是一种配对盒转录因子，在后脑和泌尿道的胚胎发生中具有基本作用。PAX 基因是原癌基因，PAX2 的表达可能有助于肾细胞癌的发病机制。由于 PAX2 在发育中的后脑中的表达及其在小脑发育中的重要作用，人们假设 PAX2 也可能参与成神经管细胞瘤的肿瘤发生。我们研究了 PAX2 和神经谱系中各种基因在成神经管细胞瘤和神经胶质瘤细胞系中的表达模式。我们发现 PAX2 mRNA 和 PAX2 蛋白在成神经管细胞瘤细胞中的高表达，以及一些神经胶质瘤细胞系中独立于其神经元谱系基因表达特征。PAX2 的基因抑制降低了 Daoy 细胞中 PAX2 转录靶标 GDNF 的表达，并在体外对 Daoy 成神经管细胞瘤和 T98G 神经胶质瘤细胞具有显著的细胞毒性作用。然后通过免疫组织化学法在两个单独的成神经管细胞瘤组织微阵列中对 61 个患者样本中的 PAX2 表达进行了评估。在大多数成神经管细胞瘤样本中检测到 PAX2 的表达，并与分化程度较低的组织学相关。因此，PAX2 是一种更具侵袭性成神经管细胞瘤表型的生物标志物，可能代表一种新的治疗靶点。
