Overexpression of aromatase leads to development of testicular Leydig celltumors - An in vivo model for hormone-mediated testicular cancer

Despite recent advances in diagnosis and treatment of testicular cancer, it s causes remain unknown. The most common conditions known to be associated with testicular cancer are cryptorchidism, infertility, and overexposure to pesticides or radiation, Recent studies also indicate hormones may play a crucial role in testicular tumorigenesis, Our studies show that about half of the male transgenic mice overexpressing aromatase in testis were inferti le and/or had larger than normal testicles, Gross pathology and histologica l analysis showed the mice to have Leydig cell tumors, unilaterally or bila terally, Serum estradiol levels for transgenic mice were at least twice as high as those for nontransgenic mice. Expression of aromatase and estrogen receptor mere also very high in testicular tissue of transgenic mice compar ed to nontransgenic mice. Consistent with increased estrogenic activity in the testicular tissue, me also sam an increase in the levels of genes invol ved in cell cycle that are regulated by the estrogen, To obtain a better un derstanding of the biological significance of testicular tumorigenesis, a r eliable animal model is necessary to clarify the mechanisms and correlation s associated with human cancers. Here we describe such a model, which shows that overexpression of aromatase results in increased estrogen production and a changed hormone milieu, leading to the induction of testicular cancer (Leydig cell tumors), This predictable and useful model is a potential too l for the study of testicular tumorigenesis, hormonal carcinogenesis, syner gistic action of other carcinogens on hormone-induced tumors, and tumor dep endency on endocrine factors.