The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene cooperatively regulate cyclin-dependent kinase 4-mediated phosphorylation of pRB in the cell cycle of normal cells. p16/CDKN2 gene and cyclin D1/PRAD-1 gene alterations have been detected in squamous cell carcinoma cell lines and in several primary squamous cell carcinomas of the esophagus. We immunohistochemically assessed p16 and cyclin D1...

The product of the p16/CDKN2 locus, p16ink4, negatively regulates the cell cycle through binding and inactivation of cyclin-dependent kinases (CDKs) 4 and 6. This locus is frequently targeted for deletion in cell lines and primary tumor tissues. In gliomas, although up to 50% do not have detectable expression of p16/CDKN2 protein or mRNA, often the gene is wild type in sequence. Here, we tested...

Tumors often display unrestricted cell cycling attributable to a dysfunctional G1-S checkpoint. One of the mechanisms leading to such a defect is the inactivation of the cyclin-dependent kinase inhibitor p16. Although inactivation of p16 is observed in a wide range of tumors, including cutaneous melanoma, genetic alteration of p16 is reportedly uncommon in uveal melanoma. Here we show that the ...

To explore the role of p16(INK4a) as an intrinsic barrier to B cell transformation by EBV, we transformed primary B cells from an individual homozygous for a deletion in the CDKN2A locus encoding p16(INK4a) and p14(ARF). Using recombinant EBV-BAC viruses expressing conditional EBNA3C (3CHT), we developed a system that allows inactivation of EBNA3C in lymphoblastoid cell lines (LCLs) lacking act...

The p16(INK4a)-Rb tumour suppressor pathway is required for the initiation and maintenance of cellular senescence, a state of permanent growth arrest that acts as a natural barrier against cancer progression. Senescence can be overcome if the pathway is not fully engaged, and this may occur when p16(INK4a) is inactivated. p16(INK4a) is frequently altered in human cancer and germline mutations a...

CDKN2/p16 inhibits the cyclin D/cyclin-dependent kinase complexes that phosphorylate pRb, thus blocking cell cycle progression. We previously reported that p16 levels are low to undetectable in normal human uroepithelial cells (HUCs) and in immortalized uroepithelial cells with functional pRb, whereas p16 levels are markedly elevated in immortal HUCs with altered pRb (T. Yeager et al., Cancer R...

Familial melanoma is associated with point mutations in the cyclin-dependent kinase (CDK) inhibitor p16(INK4A) (p16). We recently reported that p16 regulates intracellular oxidative stress in a cell cycle-independent manner. Here we constructed 12 different familial melanoma-associated point mutants spanning the p16 coding region and analyzed their capacity to regulate cell cycle phase and supp...

This study investigated the influence of expression of proteins of the INK4 family, particularly p16, on the growth and self-renewal kinetics of hematopoietic cells. First, retrovirus-mediated gene transfer (RMGT) was used to restore p16(INK4a) expression in the p16(INK4a)-deficient lymphoid and myeloid cell lines BV173 and K562, and it was confirmed that this inhibited their growth. Second, to...

AIMS To evaluate the clinicopathological significance of p16 expression in the surgical management of squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx, and larynx. METHOD p16 expression in 225 head and neck squamous cell carcinomas (HNSCCs) was studied using an immunohistochemical method and paraffin wax embedded tumour tissues. Associations between p16 expression and clin...

The helix-loop-helix transcription factor Id1 coordinates cell growth and differentiation pathways within mammalian cells and has been implicated in regulating G(1)-S phase cell cycle transitions. Recently Id1 has been shown to repress Ets- and E-protein-mediated transactivation of p16/Ink4a. Because the p16/Ink4a protein has been demonstrated to be inactivated in subsets of familial and sporad...