Lack of p19INK4d in human testicular germ-cell tumours contrasts with high expression during normal spermatogenesis.
p19INK4d, a member of the INK4 family of cyclin-dependent kinase inhibitors, negatively regulates the proto-oncogenic cyclin D/CDK4(6) complexes whose ability to phosphorylate the retinoblastoma tumour suppressor (RB) promotes G1/S transition. In contrast to the related p16INK4a tumour suppressor, expression patterns of 19INK4d in human tissues and tumours remain unknown. As the RB pathway is commonly targeted in cancer, and mouse models suggest a role for p19INK4d in spermatogenesis, we examined the abundance and localization of p19INK4d in the human testis, both during normal development and at various stages of germ-cell tumour pathogenesis. Our data show that the p19INK4d protein is abundant in spermatocytes of normal human adult testes, whereas virtually no p19INK4d is detectable in testicular cancer, including the preinvasive carcinoma in situ stage. Together with the lack of p19INK4d in human foetal germ cells, these results support the concept of foetal origin of the testicular germ-cell tumours, and help better understand the emerging role of the RB pathway in spermatogenesis and tumorigenesis in the human testis. Oncogene (2000) 19, 4146 - 4150
Bartkova
J
J
Danish Cancer Society, Institute of Cancer Biology, Strandboulevarden 49, DK-2100 Copenhagen O, Denmark.
Thullberg
M
M
Rajpert-De Meyts
E
E
Skakkebaek
N E
NE
Bartek
J
J
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D056742:Cyclin D2; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050764:Cyclin-Dependent Kinase Inhibitor p19; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D016213:Cyclins / Q000037:antagonists & inhibitors / Q000235:genetics; D005333:Fetus; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D018237:Germinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011518:Proto-Oncogene Proteins; D013091:Spermatogenesis / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
C080336:CCND2 protein, human; C493974:CDKN2D protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056742:Cyclin D2; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050764:Cyclin-Dependent Kinase Inhibitor p19; D016213:Cyclins; D011518:Proto-Oncogene Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases