iciency of Splicing Factor 1 Suppresses the Occurrence of R ticular Germ Cell Tumors

Download ticular germ cell tumors (TGCT) originate from germ cells. The 129-Ter and M19 (129.MOLF-Chr19 mic) mouse strains have extremely high incidences of TGCTs. We found that the expression levels of coded splicing factor 1 (SF1) can modulate the incidence of TGCTs. We generated mice with inactivated null mice (Sf1−/−) died before birth. Mice with one intact allele of Sf1 (Sf1+/−) were viable but expressed d levels of Sf1. When Sf1-deficient mice (Sf1+/−) were crossed to the 129-Ter and M19 strains, we obdecreased incidence of TGCTs in Sf1+/−;Ter and Sf1+/−;M19/+ mice compared with that in control ts. Therefore, Sf1 deficiency protects against TGCT development in both strains. Sf1 is expressed in stes. We found that Sf1 levels vary significantly in the testes of inbred strains such as 129 and MOLF, such Sf1 is an oncogenic tumor-susceptibility factor from 129. Our results also highlight the complicanvolved in evaluating Sf1 levels and TGCT incidences. When a large number of tumor-promoting factors esent in a strain, the protective effect of lower Sf1 levels is masked. However, when the dosage of tumorting factors is reduced, the protective effect of lower Sf1 levels becomes apparent. SF1 is involved in g of specific pre-mRNAs in cells. Alternate splicing generates the complex proteosome in eukaryotic splicin cells. Our data indicate that Sf1 levels in mouse strains correlate with their incidences of TGCTs and implicate the importance of splicing mechanisms in germ cell tumorigenesis. Cancer Res; 70(18); 7264–72. ©2010 AACR.