RT-PCR-based tyrosine kinase display profiling of canine melanoma: IGF-1 receptor as a potential therapeutic target

Melanoma Research
Douglas H ThammIlene D Kurzman

Abstract

Canine malignant melanoma (CMM) resembles human malignant melanoma in terms of metastatic behavior, refractoriness to standard therapy, and tumor antigen expression but it is largely unknown how CMM resembles human melanoma with regard to molecular pathogenesis and cellular signaling. No attempt has been made to systematically define the repertoire of tyrosine kinases (TKs) expressed in CMM. This study used a reverse transcription-PCR display technique to evaluate the expression of multiple TKs in the 17CM98 CMM cell line. RT-PCR was performed using degenerate primers coding for highly conserved regions flanking the kinase domains of many TKs and the repertoire of TKs expressed was determined using standard molecular cloning techniques. Sequencing 46 clones yielded canine homologs of insulin-like growth factor-1 receptor (IGF-1R) (50%), JAK1 (17%), PDGFR-a (11%), FGFR1 (9%), Axl (7%), Abl (4%), and PTK2 (2%). Interestingly, IGF-1R, JAK1, and Axl were detected in human melanoma using similar techniques, supporting the cross-species validity of this assay. Given the abundance of IGF-1R clones, we determined the biological effect of rhIGF-1 in 17CM98 cells. IGF-1 stimulated cell proliferation and vascular endothelial growth factor...Continue Reading

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Aug 19, 2011·Veterinary and Comparative Oncology·K C KennedyD H Thamm
Jan 23, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Eduardo LabordaRamon Alemany
Jun 6, 2013·Veterinary Pathology·C CampagneG Egidy
Feb 23, 2018·Veterinary Medicine and Science·Linda RhodesErnst Heinen
Nov 5, 2010·Current Opinion in Supportive and Palliative Care

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