2052

It has been reported that the Sonic Hedgehog (Shh) pathway is not only crucial for early embryonic development but also for stem cell maintenance leading to tumor progression (e.g. medulloblastoma).

In this study we performed semiquantitative RT-PCR of four Shh pathway genes (Patch1, Smo, Gli1 and Gli3) before and after treatments with 5-azacytidine and Trichostatin A (TSA) in six medulloblastoma cell lines, eight glioblastoma cell lines and eleven neuroblastoma cell lines. Also, methylated specific qPCR of the Smo gene was performed in six medulloblastoma cell lines, eight glioblastoma cell lines, and sixty tumor samples (forty glioblastomas and twenty neuroblastomas).

Our results indicate good expression of these genes in all three tumor cell lines (see Table 1), only Patch1 showing re-expression in medulloblastoma cell lines. We also found no medulloblastoma cell line showed Smo methylation, while one glioblastoma cell line -U87MG- and 60% (24/40) glioblastomas and 20% (8/20) neuroblastoma samples showed methylation in the Smo promoter region.

Taken together, these data indicate that 1) Shh has a role in glioblastoma and neuroblastoma progression, and not only in medulloblastoma, 2) Smo expression is needed for Gli3 expression in medulloblastoma and glioblastoma cell lines, but not in neuroblastoma cell lines, and 3) hemimethylation in the promoter region of the Smo gene in glioblastoma and neuroblastoma might not be enough to silence the gene.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA