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Promotion of Seminomatous Tumors by Targeted Overexpression of Glial Cell Line-derived Neurotrophic Factor in Mouse Testis¹

Developmental Biology [X. M., K. W., H. S.] and Molecular Neurobiology Research Programs [M. S.], Institute of Biotechnology, Viikki Biocenter, FIN-00014 University of Helsinki, Finland; HUCS Diagnostics and Department of Biomedicine, FIN-00014 University of Helsinki, Finland [H. S.]; and Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands [D. G. d. R.]

We show with transgenic mice that targeted overexpression of glial cell line-derived neurotrophic factor (GDNF) in undifferentiated spermatogonia promotes malignant testicular tumors, which express germ-cell markers. The tumors are invasive and contain aneuploid cells, but no distant metastases have been found. By several histological, molecular, and histochemical characteristics, the GDNF-induced tumors mimic classic seminomas in men, representing a useful experimental model for testicular germ-cell tumors. The data also show that a deregulated stimulation of a normal proto-oncogene by its ligand can be an initiative event in carcinogenesis.

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