Metastasizing Neuroblastomas from Taste Buds in Rats Transgenic for the Simian Virus 40 Large T Antigen under Control of the Probasin Gene Promoter

Abstract

During establishment of a prostate cancer model in rats transgenic for the Simian virus 40 large T antigen, under control of the probasin gene promoter, with protein expression specific to the prostate, tongue, and spinal cord, undifferentiated small round cell tumors were frequently observed. Extensive examination of tongues of the transgenic rats, despite a macroscopically normal appearance, revealed the tumors to have come from taste buds of the papilla circumvallata and papilla foliata. The lesions were positive for the SV40 T antigen, PGP9.5 (ubiquitin C-terminal hydrolase), and synaptophysin, neuron and neuroendocrine markers. Morphologically and immunohistochemically, the tumors were diagnosed as neuroblastomas, considering the neuroepithelial origin. Histologically identical tumor cells in the spinal cord and lung were observed only in the rats with deeply invading tongue tumors, suggesting that metastasis from the tongue tumors had occurred. Castration or supplementation with testosterone propionate did not alter tumor development, indicating the tumors to be androgen-independent . These results clearly show that taste buds can give rise to metastasizing neuroblastomas.