The relationship between HPV and p16 immunoreactivity in these neoplasms was also investigated, as it is generally assumed that in cervical neoplasms diffuse p16 expression is predictive of the presence of high-risk HPV.
Thus we propose that phosphorylation of ARF in both immortalized and tumor cell lines could be a mechanism to escape ARF surveillance following proliferative and oncogenic stress.
Inhibition of DUB-activity mediated by these compounds downregulates cell-cycle promoters, e.g., cyclin D1 and upregulates tumor suppressors p53, p27(Kip1) and p16(Ink4A).
We previously found p16 promoter methylation in DNA in the sera of 13 colorectal cancer patients out of 44 (30%) whose tumor DNA exhibited the methylation, using methylation-specific PCR (MSP).
Analysis of mutations with immune markers revealed that ADCY8 and PIK3CA mutations were associated with markedly decreased tumoral PD-L1 expression, LUSCs with PIK3CA mutations exhibited elevated CD45ro levels and CDKN2A-mutant tumors displayed an up-regulated immune response.
This pathway was recapitulated by deregulated Wnt/T-cell factor signaling, with elevation of the tumor suppressor p14ARF, and reduced expression of the p53 antagonist, MDM2.
When dichotomizing PD-L1 at 1%, the p16 and Ki-67 staining percentages were two predictors for PD-L1 expression with ORs of 11.41 (p = 0.035) and 757.77 (p = 0.045). p16 and Ki-67 staining percentages and several PET/CT-derived textural features can provide supplemental information to determine tumor PD-L1 expression in HNCs.
Partial rather than complete p16/CDKN2 methylation was detected in 24% (10 of 42) of the gliomas, regardless of tumor grade, but was not observed in normal brain (0 of 10).
The cell-cycle regulatory gene INK4A-ARF (CDKN2A) has two alternative transcripts that produce entirely different proteins, namely p14(ARF) and p16, which have complementary functions as regulators of p53 and pRB tumor suppressor pathways, respectively.
In fact K-ras point mutations were frequently recognised in tumors at early stage while p16(INK4A) inactivation prevailed in tumors at advanced stage ( P=0.0063).
Overall, the data suggest a direct role for ARF haploinsufficiency in melanoma predisposition and co-operation between ARF and CDKN2A in tumour formation, consistent with recent observations in Cdkn2a-specific knockout mice.
The INK4a-ARF locus encodes two tumor suppressor proteins involved in cell-cycle regulation, p16INK4a and p14ARF, whose functions are inactivated in many human cancers.
We used quantitative real-time PCR (RTQ-PCR) to determine copy number of p15, of p14(ARF) exon 1beta, and p16 exon 2 in 22 tumor cell lines and 83 bladder tumors, some of which had been assessed previously by duplex PCR.
Along these lines, activation of tumor suppressor mechanisms that inhibit the cell cycle (e.g. p16(INK4a) and p53) in response to DNA damage and other age-promoting stimuli has taken center stage in immune-aging research.
Poorly differentiated colorectal adenocarcinomas show higher rates of microsatellite instability and promoter methylation of p16 and hMLH1: a study matched for T classification and tumor location.
The methylation of the p16 gene promoter could significantly reduce p16 expression, losing its tumor suppressor activity and promoting the development of cervical cancer.