Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization

Sonic Hedgehog regulates Hes1 through a novel mechanism that is independent of canonical Notch pathway signalling

“…Medulloblastoma arising in heterozygous Patched knockout mice displays elevated expression of a number of Notch pathway genes (Yokota et al, 2004;Dakubo et al, 2006), as do similar tumours arising in mice expressing an oncogenic form of Smo (Hallahan et al, 2004). Similar findings are seen in human patients, including the upregulation of Hes1 in a subset of medulloblastoma (Fan et al, 2004;Hallahan et al, 2004).…”

Identification of candidate tumor suppressor genes inactivated by promoter methylation in melanoma

“…ENC1 is highly expressed in adult brain and spinal cord, and in numerous cell lines derived from nervous system tumors low mRNA levels were detectable (Hernandez et al, 1998). Although initially described as a TSG in neuroblastoma, high levels of ENC1 expression have been described in medulloblastoma (Yokota et al, 2004), parathyroid adenomas (Forsberg et al, 2005), hairy cell leukemia (Hammarsund et al, 2004), glioblastomas and astrocytomas (Kim et al, 2000), and colon cancer (Fujita et al, 2001), indicating that it may more commonly function in an oncogenic manner if inappropriately expressed. In our study, ENC1 was highly expressed in melanocytes while its expression was decreased in melanoma cell lines in parallel with a high methylation percentage.…”

Canonical Notch signaling is not required for the growth of Hedgehog pathway-induced medulloblastoma

“…2004; Yokota et al, 2004;Dakubo et al, 2006). Notch signaling is well recognized to influence neuronal and glial differentiation in the cerebellum.…”

“…Other ligands, receptors and targets (Jag1, Jag2, Dll1, Dll3, Notch3, Notch4, Hes1, Hes5) are also expressed in the developing cerebellum (Stump et al, 2002;Gazit et al, 2004;Irvin et al, 2004;Weller et al, 2006). A number of studies have noted dysregulation of Notch pathway components in both human and murine medulloblastoma (Berman et al, 2002;Hallahan et al, 2004;Yokota et al, 2004;Dakubo et al, 2006) including the transcription factor targets Hes1 and Hes5, and the expression of Hes1 is associated with poor clinical outcome (Fan et al, 2004). Medulloblastoma cell lines treated with g-secretase inhibitors that block Notch receptor endoproteolysis display reduced growth, clonogenicity and tumorigenicity (Hallahan et al, 2004;Fan et al, 2006).…”