Hedgehog signalling in medulloblastoma, glioblastoma and neuroblastoma.
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.
Shahi
Mehdi H
MH
Unidad de Biología de Tumores Cerebrales, Universidad de Navarra, 31008 Pamplona, Spain.
Lorente
Aiala
A
Castresana
Javier S
JS
D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D015513:Oncogene Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1