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GDNF‐induced seminomatous tumours in mouse – an experimental model for human seminomas?
Author(s) -
SARIOLA HANNU,
MENG XIAOJUAN
Publication year - 2003
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1034/j.1600-0463.2003.11101231.x
Subject(s) - glial cell line derived neurotrophic factor , biology , neurotrophic factors , sertoli cell , germ cell , germline , receptor , genetically modified mouse , testicle , endocrinology , cancer research , microbiology and biotechnology , transgene , medicine , spermatogenesis , genetics , gene
Glial‐cell‐line‐derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor superfamily. It binds to and activates a receptor complex consisting of GFR‐α1 and Ret receptor tyrosine kinase. In testis, GDNF is expressed by Sertoli cells. We have shown by transgenic loss‐ and gain‐of‐function mouse models that GDNF regulates the cell fate decision of undifferentiated spermatogonia. In the GDNF +/− mice, the spermatogonia differentiate in excess leading to the depletion of germ cells. In the mice overexpressing GDNF in testes, undifferentiated spermatogonia accumulate in the tubules, no sperm is produced, and the mice are infertile. After a year, the GDNF overexpressing mice frequently (89%) develop testicular tumours, and most of them are bilateral (56%). All these tumours show the same histological pattern. They are composed of round spermatogonial/gonocytic cells with only a scant cytoplasm. The tumours are locally invasive but do not metastasise. They express germ line markers, are positive for alkaline phosphatase, and aneuploid with a triploid peak. Thus, by several histological, molecular, and histochemical characteristics, the GDNF‐induced tumours mimic classical seminomas in men, but the precursor lesions are apparently different in mouse and man.