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...

The open reading frame III of Borna disease virus (BDV) codes for a protein with a mass of 16 kDa, named p16 or BDV-M. p16 was described as an N-glycosylated protein in several previous publications and therefore was termed gp18, although the amino acid sequence of p16 does not contain any regular consensus sequence for N glycosylation. We examined glycosylation of p16 and studied its membrane ...

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the lethal cancers with a high incidence rate in Asia. Many genes including cyclin D1 and p16 play important role in its carcinogenesis. We aimed to analyze the expressions of cyclin D1 and p16 with the various clinicopathological characteristics of ESCC. METHODS We examined 30 biopsy samples of ESCC for cyclin D1 and p16 protein ex...

Purpose Adenoid cystic carcinoma (ACC) in the lacrimal gland is a rare malignancy. P16 is encoded by the CDKN2A gene, which is recognized as a tumor suppressor due to its inactivation in many types of tumors. However, p16 overexpression is also linked to adverse tumor parameters. These contradictory observations have also been confirmed in ACCs in the salivary glands. Furthermore, evidence of h...