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Transcriptome and proteome analysis of tyrosine Kinase inhibitor treated canine mast cell tumour cells identifies potentially kit signaling-dependent genes.
Klopfleisch, Robert ;  Meyer, Anja ;  Schlieben, Patricia ;  Bondzio, Angelika ;  Weise, Chris ;  Lenze, Dido ;  Hummel, Michael ;  Einspanier, Ralf ;  Gruber, Achim D

HaupttitelTranscriptome and proteome analysis of tyrosine Kinase inhibitor treated canine mast cell tumour cells identifies potentially kit signaling-dependent genes.
AutorKlopfleisch, Robert
AutorMeyer, Anja
AutorSchlieben, Patricia
AutorBondzio, Angelika
AutorWeise, Chris
AutorLenze, Dido
AutorHummel, Michael
AutorEinspanier, Ralf
AutorGruber, Achim D
Seitenzahl[26 S.]
Freie SchlagwörterKIT; Mast cell tumor; Dog; 2D-DIGE; MALDI; Mastocytosis; Tyrosine kinase inhibition
DDC630 Landwirtschaft, Veterinärmedizin
Auch erschienen inBMC Vet Res. 2012 Jun 29;8(1):96
ZusammenfassungBackground
Canine mast cell tumor proliferation depends to a large extent on the activity of KIT, a tyrosine kinase receptor. Inhibitors of the KIT tyrosine kinase have recently been introduced and successfully applied as a therapeutic agent for this tumor type. However, little is known on the downstream target genes of this signaling pathway and molecular changes after inhibition.

Results
Transcriptome analysis of the canine mast cell tumor cell line C2 treated for up to 72 hours with the tyrosine kinase inhibitor masitinib identified significant changes in the expression levels of approximately 3500 genes or 16% of the canine genome. Approximately 40% of these genes had increased mRNA expression levels including genes associated with the pro-proliferative pathways of B- and T-cell receptors, chemokine receptors, steroid hormone receptors and EPO-, RAS and MAP kinase signaling. Proteome analysis of C2 cells treated for 72 hours identified 24 proteins with changed expression levels, most of which being involved in gene transcription, e.g. EIA3, EIA4, TARDBP, protein folding, e.g. HSP90, UCHL3, PDIA3 and protection from oxidative stress, GSTT3, SELENBP1.

Conclusions
Transcriptome and proteome analysis of neoplastic canine mast cells treated with masitinib confirmed the strong important and complex role of KIT in these cells. Approximately 16% of the total canine genome and thus the majority of the active genes were significantly transcriptionally regulated. Most of these changes were associated with reduced proliferation and metabolism of treated cells. Interestingly, several pro-proliferative pathways were up-regulated, which may represent attempts of masitinib treated cells to activate alternative pro-proliferative pathways. These pathways may contain hypothetical targets for a combination therapy with masitinib to further improve its therapeutic effect.
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Fachbereich/EinrichtungFB Veterinärmedizin
Arbeitsbereich/InstitutInstitute of Veterinary Pathology
Erscheinungsjahr2012
Dokumententyp/-SammlungenWissenschaftlicher Artikel
SpracheEnglisch
Rechte Creative Commons License
Dieses Werk ist unter einer Creative Commons-Lizenz lizenziert.
Erstellt am26.10.2012 - 10:45:46
Letzte Änderung24.03.2013 - 14:27:32
 
Statische URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000014873
DOI10.1186/1746-6148-8-96
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