Messenger RNA levels of oncogenic tyrosine kinases were determined in canine mammary tumours using real-time RT-PCR. The following tyrosine kinases and vascular endothelial growth factors (VEGF) were examined in malignant and healthy mammary tissues of 13 dogs: VEGFR1, VEGFR2, EGFR, ErbB2, PDGFR1, c-KIT and c-MET. Expression levels of all these factors were significantly higher in tumour samples than in normal mammary tissues taken from the same animal. Higher grading was associated with higher VEGFR1 levels. Grade III tumours showed significantly higher VEGF, c-MET and c-KIT mRNA expression, while Grade I tumours with lower malignancy showed significantly higher PDGFR1 and EGFR expression than tumours classified as Grade II or III. The increased presence of VEGF, VEGFR1, c-KIT and c-MET is a negative prognostic factor as these signal transduction molecules contribute to increased tumour malignancy. The presented data provide evidence, for the first time, for the existence of a complex overexpression and dysregulation of VEGF and several oncogenic tyrosine kinases such as VEGR1, PDGFR1, c-KIT and c-MET in canine mammary tumours. Therefore, canine mammary tumours may be potential targets for tyrosine kinase inhibitor therapy.
Keywords: Canine mammary tumour; chemotherapy; real-time RT-PCR; receptor tyrosine kinases.