We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Met interacts with EGFR and Ron in canine osteosarcoma.
- Authors
McCleese, J. K.; Bear, M. D.; Kulp, S. K.; Mazcko, C.; Khanna, C.; London, C. A.
- Abstract
The receptor tyrosine kinase ( RTK) Met is known to be over-expressed in canine osteosarcoma ( OSA). In human cancers, the RTKs Met, epidermal growth factor receptor ( EGFR) and Ron are frequently co-expressed and engage in heterodimerization, altering signal transduction and promoting resistance to targeted therapeutics. We found that EGFR and Ron are expressed in canine OSA cell lines and primary tissues, EGFR and Ron are frequently phosphorylated in OSA tumour samples, and Met is co-associated with EGFR and Ron in canine OSA cell lines. Transforming growth factor alpha ( TGFα) and hepatocyte growth factor ( HGF) stimulation induced amplification of ERK1/2 and STAT3 phosphorylation in OSA cells and Met was phosphorylated following TGFα stimulation providing evidence for receptor cross-talk. Lastly, treatment of OSA cells with combined gefitinib and crizotinib inhibited cell proliferation in an additive manner. Together, these data support the notion that Met, EGFR and Ron interact in OSA cells and as such, may represent viable targets for therapeutic intervention.
- Subjects
PROTEIN-tyrosine kinases; OSTEOSARCOMA; EPIDERMAL growth factor receptors regulation; CELL lines; CELLULAR signal transduction; PHYSIOLOGY
- Publication
Veterinary & Comparative Oncology, 2013, Vol 11, Issue 2, p124
- ISSN
1476-5810
- Publication type
Article
- DOI
10.1111/j.1476-5829.2011.00309.x