Neurotrophin 3/TrkC-regulated proteins in the human medulloblastoma cell line DAOY.
Medulloblastoma (MB) is the most common malignant childhood brain tumor and high neurotrophin (NP) receptor TrkC mRNA expression was identified as a powerful independent predictor of favorable survival outcome. In order to determine downstream effector proteins of TrkC signaling, the MB cell line DAOY was stably transfected with a vector containing the full-length TrkC cDNA sequence or an empty vector control. A proteomic approach was used to search for expressional changes by two mass spectrometric methods and immunoblotting for validation of significant results. Multiple time points for up to 48 h following NP-3-induced TrkC receptor activation were chosen. Thirteen proteins from several pathways (nucleoside diphosphate kinase A, stathmin, valosin-containing protein, annexin A1, dihydropyrimidinase-related protein-3, DJ-1 protein, glutathione S-transferase P, lamin A/C, fascin, cofilin, vimentin, vinculin, and moesin) were differentially expressed and most have been shown to play a role in differentiation, migration, invasion, proliferation, apoptosis, drug resistance, or oncogenesis. Knowledge on effectors of TrkC signaling may represent a first useful step for the identification of marker candidates or reflecting probable pharmacological targets for specific treatment of MB.
Gruber-Olipitz
Mariella
M
Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
Ströbel
Thomas
T
Kang
Sung Ung
SU
John
Julius Paul Pradeep
JP
Grotzer
Michael A
MA
Slavc
Irene
I
Lubec
Gert
G
D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000175:diagnosis / Q000378:metabolism*; D020812:Receptor, trkC / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D014408:Biomarkers, Tumor; D020812:Receptor, trkC