Increased p16 Levels Correlate with pRb Alterations in Human Urothelial Cells

摘要: The CDKN2 (MTS1) gene is located at 9p21; its product, p16, inhibits the cyclin D/CDK4 complex that phosphorylates pRb, thus negatively regulating cell cycle progression [M. Serrano et al. , Nature (Lond.), 366: 704, 1994; A. Kamb Science (Washington DC), 264: 436, T. Nobori 368: 753, 1994]. mutations are more common in cultured human uroepithelial cells (HUC) than uncultured bladder cancers. We examined status of CDKN2/p16 early and late passage (P) cultures HUC. HUC immortalization was not accompanied by p16 loss, even with a hemizygous 9p21-pter deletion, but loss showed decreased generation time. Thus, data do indicate candidate for chromosome 9 senescence suggest may confer growth advantage vitro . Significant differences levels were observed among lines, no detected. However, an inverse correlation between elevated pRb function ( P < 10-4). Ten samples normal low or undetectable levels, while seven known alterations abundant nevertheless grew vigorously culture. These results support hypothesis mediated inhibition, as well regulation, occurs via dependent pathway(s).