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Activated Notch pathway proteins and FoxG1 are co‐expressed in Medulloblastoma: correlation with phenotype
Author(s) -
Peters L,
Mehta V,
Chintagumpala M,
Dauser R,
Adesina A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.706.41
Subject(s) - hes1 , notch signaling pathway , biology , medulloblastoma , phenotype , cancer research , repressor , effector , signal transduction , microbiology and biotechnology , transcription factor , genetics , gene
Notch pathway activation has been implicated in the negative regulation of neural differentiation in the developing central nervous sytem. Hes 1 and Hes 5 are downstream effectors of the Notch pathway. FoxG1 forms a transcriptional repressor complex with Hes1 and was recently reported as dysregulated in all histologic types of medulloblastoma. We examined 64 medulloblastomas by IHC for nuclear expression of activated Notch‐1, Hes1, and Hes5. Activated Notch‐1, Hes1, and Hes5 expression were detected in all histologic subtypes. Using Spearman correlation (SC) analysis, there was a positive correlation between the expression of activated Notch1 and Hes1 (SC coeff 0.36, p=0.0035) and Hes 5 (SC coeff 0.433, p<0.001). Expression of FoxG1 and Notch1 also showed a weak, but significant positive correlation (SC coeff 0.273, p=0.028). Activated Notch1 expression was higher in the anaplastic subtype (ANOVA on Ranks, Dunn's test, H=12.968, p=0.002). Co‐expression of FoxG1 and Notch pathway effectors is consistent with a putative combined role of FoxG1 and activated Notch pathway in the maintenance of an undiferentiated state in medulloblastoma. In view of the reported association of myc amplification with anaplastic progression and the known Notch‐Wnt signaling pathway crosstalk, the significance of our demonstration of a correlation between Notch1 expression and the anaplastic phenotype remains to be explored.