Koltai Zsófia, Szabó Bernadett, Jakus Judit, Vajdovich Péter
1 Veterinary Haematology and Oncology Centre , Bolgárkertész u. 31, H-1148 Budapest , Hungary.
2 Department of Clinical Pathology and Oncology, University of Veterinary Medicine , Budapest , Hungary.
Acta Vet Hung. 2018 Jun;66(2):294-308. doi: 10.1556/004.2018.027.
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.
利用实时逆转录聚合酶链反应(RT-PCR)测定犬乳腺肿瘤中致癌性酪氨酸激酶的信使核糖核酸(mRNA)水平。在13只犬的恶性和健康乳腺组织中检测了以下酪氨酸激酶和血管内皮生长因子(VEGF):血管内皮生长因子受体1(VEGFR1)、血管内皮生长因子受体2(VEGFR2)、表皮生长因子受体(EGFR)、ErbB2、血小板衍生生长因子受体1(PDGFR1)、原癌基因c-KIT和肝细胞生长因子受体(c-MET)。所有这些因子在肿瘤样本中的表达水平均显著高于取自同一动物的正常乳腺组织。更高的分级与更高的VEGFR1水平相关。III级肿瘤显示VEGF、c-MET和c-KIT的mRNA表达显著更高,而恶性程度较低的I级肿瘤显示PDGFR1和EGFR的表达显著高于II级或III级肿瘤。VEGF、VEGFR1、c-KIT和c-MET的增加是一个负面预后因素,因为这些信号转导分子会导致肿瘤恶性程度增加。所呈现的数据首次证明了在犬乳腺肿瘤中存在VEGF和几种致癌性酪氨酸激酶(如VEGR1、PDGFR1、c-KIT和c-MET)的复杂过表达和失调。因此,犬乳腺肿瘤可能是酪氨酸激酶抑制剂治疗的潜在靶点。