SUBCUTANEOUS SARCOMAS OF PROBABLE NEURONAL ORIGIN IN A TRANSGENIC MOUSE STRAIN CONTAINING AN ALBUMIN PROMOTER-FUSED SIMIAN-VIRUS-40 LARGE T-ANTIGEN GENE

Frequent development of subcutaneous neurogenic sarcomas was observed in a hepatocellular carcinoma-producing transgenic mouse strain harbor ing an albumin-promoted simian virus 40 (SV40) large T antigen gene. F ound unexpectedly in 19 out of 306 mice (6.2%) by 6 months of age, all the sarcomas were similar and were characterized as neurogenic on the basis of histological features including Homer-Wright type rosette fo rmation, the presence of dense core granules of 100-200 nm diameter un der the electron microscope, expression of neuron specific enolase, S- 100 protein, and catecholamines, and nerve cell-like differentiation i n culture in response to But2cAMP. Immunohistochemical study revealed tiny clusters of SV40 T antigen-expressing cells with neurogenic chara cter in normal-appearing adult mouse subcutis as candidate progenitors of the sarcomas. The tumor cells strongly expressed large T antigen b ut did not express albumin or albumin mRNA at the detection sensitivit y used. Transient transfection assay (CAT assay), however, revealed th e presence of transcriptional factor(s) acting on the albumin promoter in tumor cells. Thus, the present investigation suggested the presenc e of specifically differentiated neurogenic cells in the mouse subcuti s with aberrant expression of the transgene.