Tissue specificity of oncogene action: endothelial cell tumours in polyoma middle T transgenic mice

Newborn mice inoculated with murine polyoma (Py) virus develop tumours in a wide range of tissues. To investigate viral oncogenesis we have generated transgenic mice carrying either the Py large T antigen (LT) gene or the Py middle T antigen (MT) gene linked to Py early regulatory sequences. Some Py LT mice develop pituitary tumours, while Py MT mice develop multifocal tumours of the vascular endothelium. These haemangiomas are lethal to the animals and can be passaged in vivo. Transgene RNAs and protein are present in both haemangiomas and the testes of these mice, and the Py middle T protein in both tissues is complexed to a cellular tyrosine kinase. The expression of complexed middle T protein in both tumorigenic endothelial cells and in unperturbed testes implies that endothelial cells may be particularly susceptible to the action of the middle T oncogene. The idea that oncogenes may exhibit a tissue specificity in their action is supported by other transgenic mouse models of oncogenesis and by studies of human tumours.