Molecular phenotype of simian virus 40 large T antigen-induced primitive neuroectodermal tumors in four different lines of transgenic mice.

We compared the molecular phenotypes of central nervous system tumors arising in four different lines of transgenic mice (TGM) carrying the Simian virus 40 large T antigen driven by different promoters or enhancers. Two of the four lines developed primitive neuroectodermal tumors (PNETs) in the brain stem or pineal gland. A third TGM line developed retinoblastomas (a PNET-like tumor of the retina) as well as PNETs in the mesencephalon, while the fourth TGM developed retinoblastomas and adrenal pheochromocytomas. The expression of developmentally regulated polypeptides specific for the neuronal or glial lineage was examined in these PNETs using immunohistochemistry and Western blotting. Neoplastic cells in all of the PNETs exhibited neuronal, but no glial specific markers as evidenced by the invariable expression of synaptophysin, but no detectable glial fibrillary acidic protein or myelin basic protein. PNETs with a more differentiated neuronal phenotype expressed multiple neuronal polypeptides. The phenotypic properties of these PNETs closely resembled those found in human brain PNET biopsy samples and cell lines derived therefrom. We conclude that Simian virus 40 T antigen-induced PNETs in TGM exhibit the molecular phenotype of developing neurons or neuronal progenitor cells. Although many factors could influence the phenotype of these experimental PNETs (e.g., promoter, site of integration of the transgene) these PNETs appear to be suitable TGM models of human PNETs of the central nervous system.