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The expression of the EGF receptor family and their ligands in human medulloblastomas
Author(s) -
Collins V. P.,
Ichimura K.,
Liu L.
Publication year - 2002
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1046/j.1365-2990.2002.39286_24.x
Subject(s) - juxtacrine signalling , biology , autocrine signalling , erbb4 , cancer research , paracrine signalling , medulloblastoma , wnt signaling pathway , epidermal growth factor , erbb , patched , receptor , hedgehog signaling pathway , medicine , microbiology and biotechnology , signal transduction , genetics , receptor tyrosine kinase
Little is known about the molecular processes behind the development of medulloblastomas. While many chromosomal abnormalities have been more or less consistently observed, only a few cellular pathways have been identified as being targeted. These include the Hedgehog/patched signalling pathway (involving PTCH, PTCH2, SSH and SMOH) and the Wnt signalling pathway (involving APC, and β‐catenin). Amplification of N‐myc is associated with a bad prognosis. Material and methods: We examined the expression of the Epidermal Growth Factor Receptor family and nine of their ligands in a series of 48 medulloblastomas and supratentorial primitive neuroectodermal tumours (PNETs) by quantitative RT‐PCR, Western blot and immunocytochemistry. Results: The most striking finding was the high levels of expression of erbB4 transcript – in some cases greater that 250 times that found in normal cerebellum. ErbB4 transcript levels greater than 10 times that of cerebellum were seen in 73% of the series. ErbB2 and erbB3 transcript levels exceeding 10 times that of cerebellum were seen in 35% of cases. Only two cases had overexpression of EGFR/erbB1 at these levels. Ligands (Epiregulin/Betacellulin/NDF_/NDF_1/NDF_2) for erbB4 were coexpressed in 74% (26/35) of the cases with high erbB4 expression. Only one case showed no expression of erbB4 and its ligands. Conclusions: The findings suggest that various forms of autocrine, paracrine, and juxtacrine stimulation through these receptors may contribute to the malignant phenotype of medulloblastomas.