Analysis of the TEL protein during tumour angiogenesis.

It has been proposed that breast cancer follows a programmed course of development that leads to an invasive phenotype that is associated with an increase in angiogenesis. Angiogenesis is a multistage process that requires, at its early stages, proliferation of endothelial cells, the break-down of their basement membranes, and their subsequent migration and organisation into new bud-like vascular structures. The regulation of endothelial cell proliferation and migration during angiogenesis involves the ETS family of transcription factors. The TEL gene is a member of the ETS family and may play a role in vessel formation. Vascular endothelial growth factor (VEGF) is a specific growth factor in new vessel formation and in this study its regulatory effects on TEL protein phosphorylation are detailed. The TEL protein is found to be expressed during early endothelial cell tube formation in vitro. However, smaller vessels in either tumour or ovarian angiogenesis did not express the transcription factor; only the larger mature vessels were positive. Interestingly, TEL protein expression was lost in the invasive breast carcinoma studied, whilst in normal breast tissue, hyperplasia and ductal carcinoma in-situ, TEL protein expression was seen. The loss of expression of TEL protein in invasive mammary gland carcinoma may be an important factor in the pathogenesis of breast carcinoma.