Activation of ERK, AKT and JNK signalling pathways in human schwannomas in situ.
OBJECTIVE
Schwannomas are common tumours that may be multiple in neurofibromatosis type 2, when they may be difficult to treat without significant morbidity using surgery and radiosurgery. Previous in vitro work has suggested that merlin loss is associated with activation of the JNK/JUN, PI3K/AKT and MEK/ERK pathways and that these pathways may be susceptible to pharmacological inhibition. The aim was to investigate the expression of proteins involved in these pathways in human schwannomas in situ.


RESULTS
Immunohistochemistry using antibodies to AKT, pAKT, MEK, pMEK, ERK, pERK, JUN and pJUN was applied to 16 schwannomas (sporadic and NF2), and the results were compared with those seen in traumatic neuromas. Increased expression of pMEK, pERK and pJUN was seen in the schwannomas samples and of pAKT in schwannomas and controls.


CONCLUSIONS
These findings provide further direct evidence for activation of the JNK/JUN, PI3K/AKT and MEK/ERK signalling pathways in schwannomas and support the development of therapeutic agents directed against these pathways for the treatment of this group of tumours.
Hilton
David A
DA
Department of Neuropathology, Derriford Hospital, UK.
Ristic
Natalia
N
Hanemann
Clemens O
CO
D016543:Central Nervous System Neoplasms / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009442:Neurilemmoma / Q000378:metabolism*; D010524:Peripheral Nervous System Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases