Promotion of seminomatous tumors by targeted overexpression of glial cell line-derived neurotrophic factor in mouse testis

We show with transgenic mice that targeted overexpression of glial cell lin e-derived neurotrophic factor (GDNF) in undifferentiated spermatogonia prom otes malignant testicular tumors, which express germ-cell markers. The tumo rs are invasive and contain aneuploid cells, but no distant metastases have been found. By several histological, molecular, and histochemical characte ristics, the GDNF-induced tumors mimic classic seminomas in men, representi ng a useful experimental model for testicular germ-cell tumors. The data al so show that a deregulated stimulation of a normal proto-oncogene by its li gand can be an initiative event in carcinogenesis.