Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirus

In existing mouse models for malignant brain tumors, genes with no proven p athogenical relevance for humans have been used, Coexpression of platelet-d erived growth factor (PDGF) and PDGF receptors suggests an autocrine mechan ism of growth factor stimulation in the development of brain tumors in man. A murine retrovirus coding for the PDGF B-chain was, therefore, used to in duce brain tumors in mice. Of 35 mice who received injections, 15 developed brain tumors of oligo- or monoclonal origin. They coexpressed PDGF B-chain and alpha-receptor mRNA, as expected, from an autocrine mechanism of trans formation. Most tumors displayed characteristics of glioblastoma multiforme or of a primitive neuroectodermal tumor, and the consistent expression of nestin suggested that they were all derived from an immature neuroglial pro genitor. The results show that an autocrine mechanism of transformation may be an initial or early event in neuro-oncogenesis. The present model provi des an ideal system for studies of genetic mechanisms involved in the devel opment of brain tumors.