Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aneuploidy
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Animals
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Disease Models, Animal
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Flow Cytometry
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Glial Cell Line-Derived Neurotrophic Factor
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In Situ Hybridization
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Male
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Mice
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Mice, Transgenic
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Nerve Growth Factors / biosynthesis
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Nerve Growth Factors / genetics
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Nerve Tissue Proteins / biosynthesis*
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Nerve Tissue Proteins / genetics
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Seminoma / etiology*
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Seminoma / genetics
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Seminoma / metabolism*
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Spermatogonia / metabolism
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Testicular Neoplasms / etiology*
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Testicular Neoplasms / genetics
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Testicular Neoplasms / metabolism*
Substances
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Gdnf protein, mouse
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Glial Cell Line-Derived Neurotrophic Factor
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Nerve Growth Factors
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Nerve Tissue Proteins