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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

Main titleTranscriptome and proteome analysis of tyrosine Kinase inhibitor treated canine mast cell tumour cells identifies potentially kit signaling-dependent genes.
AuthorKlopfleisch, Robert
AuthorMeyer, Anja
AuthorSchlieben, Patricia
AuthorBondzio, Angelika
AuthorWeise, Chris
AuthorLenze, Dido
AuthorHummel, Michael
AuthorEinspanier, Ralf
AuthorGruber, Achim D
No. of Pages[26 S.]
KeywordsKIT; Mast cell tumor; Dog; 2D-DIGE; MALDI; Mastocytosis; Tyrosine kinase inhibition
Classification (DDC)630 Agriculture, Veterinary medicine
Also published inBMC Vet Res. 2012 Jun 29;8(1):96
AbstractBackground
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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FU DepartmentDepartment of Veterinary Medicine
Other affiliation(s)Institute of Veterinary Pathology
Year of publication2012
Type of documentScience article
LanguageEnglish
Terms of use/Rights Creative Commons License
Dieses Werk ist unter einer Creative Commons-Lizenz lizenziert.
Created at2012-10-26 : 10:45:46
Last changed2013-03-24 : 02:27:32
 
Static URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000014873
DOI10.1186/1746-6148-8-96
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