RNF4 is a growth inhibitor expressed in germ cells but not in human testicular tumors

The RING-finger protein RNF4 modulates both steroid-receptor-dependent and basal transcription and interacts with a variety of nuclear proteins involv ed in cell growth control. RNF4 is expressed at very high levels in. testis and at much lower levels in several other tissues. We show that in germ ce lls RNF4 expression is strongly modulated during progression of spermatogon ia to spermatids, with a peak in spermatocytes. Analysis of human testicula r germ cell tumors shows that RNF4 is not expressed in all tumors analyzed including seminomas, the highly malignant embryonal carcinomas, yolk sac, a nd mixed germ cell tumors. We also show that the ectopically expressed RNF4 gene inhibits cell proliferation of both somatic and germ cell tumor-deriv ed cells. Mutation of critical cysteine residues in the RING finger domain abolished the RNF4 growth inhibition activity. our results suggest that the lack of RNF4 expression may play a role in the progression of testicular t umors.