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 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.
Meng
X
X
Developmental Biology and Molecular Neurobiology Research Programs, Institute of Biotechnology, Viikki Biocenter, FIN-00014 University of Helsinki, Finland.
de Rooij
D G
DG
Westerdahl
K
K
Saarma
M
M
Sariola
H
H
D000782:Aneuploidy; D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D051100:Glial Cell Line-Derived Neurotrophic Factor; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D018239:Seminoma / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D013093:Spermatogonia / Q000378:metabolism; D013736:Testicular Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*
C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins