Shahi Mehdi H, Lorente Aiala, Castresana Javier S
Unidad de Biología de Tumores Cerebrales, Universidad de Navarra, 31008 Pamplona, Spain.
Oncol Rep. 2008 Mar;19(3):681-8.
We investigated a role for Hedgehog signalling in glioblastoma, neuroblastoma and medulloblastoma by studying the transcription of PTCH, SMO, GLI1 and GLI3 in a total of 25 cell lines by standard RT-PCR and qRT-PCR, before and after 5-aza-2'-deoxycytidine and trichostatin A (TSA) treatments. Also 25 glioblastoma samples were tested by qRT-PCR. We also performed real-time methylated specific PCR (qMSP) of the SMO promoter region in DNA from 80 tumor samples (40 glioblastomas and 40 neuroblastomas) and from the 25 cell lines. We detected SMO promoter methylation in more than half of the cell lines and tumor samples. PTCH expression in cell lines was lower than in normal controls, just the opposite to GLI1. SMO and GLI3 expression were high and fully correlated in glioblastoma and medulloblastoma, although partially in neuroblastoma. Our results support the existence of Hedgehog signalling in glioblastoma and medulloblastoma, and to a lesser extent, in neuroblastoma.
我们通过标准逆转录聚合酶链反应（RT-PCR）和定量逆转录聚合酶链反应（qRT-PCR），研究了25种细胞系在5-氮杂-2'-脱氧胞苷和曲古抑菌素A（TSA）处理前后PTCH、SMO、GLI1和GLI3的转录情况，以探究刺猬信号通路在胶质母细胞瘤、神经母细胞瘤和髓母细胞瘤中的作用。此外，还通过qRT-PCR对25个胶质母细胞瘤样本进行了检测。我们还对80个肿瘤样本（40个胶质母细胞瘤和40个神经母细胞瘤）以及25个细胞系的DNA中的SMO启动子区域进行了实时甲基化特异性PCR（qMSP）。我们在超过一半的细胞系和肿瘤样本中检测到了SMO启动子甲基化。细胞系中PTCH的表达低于正常对照，这与GLI1的情况相反。在胶质母细胞瘤和髓母细胞瘤中，SMO和GLI3的表达较高且完全相关，尽管在神经母细胞瘤中只是部分相关。我们的结果支持了刺猬信号通路在胶质母细胞瘤和髓母细胞瘤中存在，在神经母细胞瘤中存在程度较低。
