Lack of p19(INK4d) in human testicular germ-cell tumours contrasts with high expression during normal spermatogenesis

p19(INK4d) a member of the INK4 family of cyclin-dependent kinase inhibitor s, negatively regulates the proto-oncogenic cyclin D/CDK4(6) complexes whos e ability to phosphorylate the retinoblastoma tumour suppressor (RB) promot es G1/S transition. In contrast to the related p16(INK4a) tumour suppressor , expression patterns of 19(INK4d) in human tissues and tumours remain unkn own. As the RE pathway is commonly targeted in cancer, and mouse models sug gest a role for p19(INK4d) in spermatogenesis, ne examined the abundance an d localization of p19(INK4d) in the human testis, both during normal develo pment and at various stages of germ-cell tumour pathogenesis. Our data show that the p19(INK4d) protein is abundant in spermatocytes of normal human a dult testes, whereas virtually no p19(INK4d) is detectable in testicular ca ncer, including the preinvasive carcinoma ill situ stage. Together with the lack of p19(INK4d) in human foetal germ cells, these results support the c oncept of foetal origin of the testicular germ-cell tumours, and help bette r understand the emerging role of the RE pathway in spermatogenesis and tum origenesis in the human testis.