The receptor tyrosine kinase Tie1 is expressed and activated in epithelial tumour cell lines

Abstract

The receptor tyrosine kinase Tie1 is expressed primarily in vascular endothelial cells. The receptor has also been detected in epithelial tumours in breast, thyroid and gastric cancers and in tumour cell lines where it appears as a 45 kDa truncated receptor fragment. In this study, we show that in addition to truncated Tie1, breast and colon tumour cell lines express a full-length Tie1 holoreceptor. In contrast to the situation in endothelial cells, Tie1 truncation is not activated by phorbol esters and generation of truncated Tie1 does not occur via a metalloprotease-inhibitor sensitive mechanism. Examination of the phosphorylation status of Tie1 revealed both the holoreceptor and truncated receptor to be constitutively activated in MCF-7 cells. These data indicate that Tie1 expressed in epithelial tumour cell lines is present in holoreceptor and truncated forms, and in MCF-7 cells both forms are constitutively phosphorylated and competent to signal. Our findings suggest therefore that anti-angiogenic strategies targeting the angiopoietin/Tie system in tumour microvasculature could also have additional direct effects on the tumour epithelial cells within those tumours in which there is also extravascular expression of the Tie1 receptor tyrosine kinase.