DECREASED FAS ANTIGEN RECEPTOR EXPRESSION IN TESTICULAR-TUMOR CELL-LINES DERIVED FROM POLYOMAVIRUS LARGE T-ANTIGEN TRANSGENIC MICE

MT-PVLT-10 transgenic mice express large T-antigen of polyomavirus und er the control of the mouse metallothionein-1 promoter and males of th is transgenic line develop testicular tumors at advanced ages. The dif ferential display technique was employed to compare mRNA expression fr om immortalized cell lines derived from normal or adenomatous testis f rom MT-PVLT-10 transgenic males. Using this technique, a complementary DNA fragment corresponding to the mouse Fas antigen receptor was reco vered from normal testicular cells but not from tumor cells. RNAse pro tection assays with the Fas antigen specific fragment confirmed its di fferential expression. Normal testicular cells from the transgenic ani mals responded to treatment of interferon-gamma by increasing the expr ession of Fas antigen specific mRNA and were sensitive to the prolifer ative inhibitory effect of anti-Fas antibody in vitro. This proliferat ive inhibition was characterized by an accumulation of cells in S phas e of the cell cycle. In contrast, the testicular tumor cells did not r espond to either interferon-gamma or to anti-Fas antibody in vitro. Th ese results suggest that the loss of proliferative inhibitory effect m ediated by the Fas antigen pathway in tumor cells may be an important step in testicular tumor progression in the MT-PVLT-10 transgenic mice .