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 harboring an albumin-promoted simian virus 40 (SV40) large T antigen gene. Found 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 formation, the presence of dense core granules of 100-200 nm diameter under the electron microscope, expression of neuron specific enolase, S-100 protein, and catecholamines, and nerve cell-like differentiation in culture in response to But2cAMP. Immunohistochemical study revealed tiny clusters of SV40 T antigen-expressing cells with neurogenic character in normal-appearing adult mouse subcutis as candidate progenitors of the sarcomas. The tumor cells strongly expressed large T antigen but did not express albumin or albumin mRNA at the detection sensitivity used. Transient transfection assay (CAT assay), however, revealed the presence of transcriptional factor(s) acting on the albumin promoter in tumor cells. Thus, the present investigation suggested the presence of specifically differentiated neurogenic cells in the mouse subcutis with aberrant expression of the transgene.