HuD expression was frequently lost in many human pancreatic NETs, and these pancreatic NETs showed aggressive clinicopathological phenotypes with low p27 levels, increased tumor size, higher World Health Organization grade and pT stage of the tumor, and the presence of angioinvasion.
In this study, the expression of the cell cycle-associated proteins p16, pRb, p53, p27 and Ki-67 were examined by immunohistochemistry in precancerous and cancerous oral lesions, including verrucous carcinomas (VCs).
protein/RNA levels of β-catenin (CTNNB1), its responsive markers [CyclinD1, c-Myc], Androgen receptor (AR), p27 and class-I HDACs were measured in matched UF/MM tissues or cell populations.
Our results suggest that SKP2 has a major role in the regulation of p27 degradation and CKS1 has a supporting role for SKP2 function in human urothelial carcinoma.
We used confocal laser microscopy to examine the expression levels of pKi67, p21 and p27 in T24 cells (derived from human urothelial carcinoma) exposed six times to BCG.
The net outcome of SAG-mediated inhibition of c-Jun/AP-1 (pro-tumor promotion) and of p27 (antiproliferation) increased skin hyperplasia, with no apparent effect on apoptosis, as evidenced by increased skin thickness, and increased rate of DNA synthesis, but hardly any apoptosis.
These results reveal a tumor suppressor role of p27 in chronic hepatocyte injury-induced liver tumorigenesis and, at the same time, the need to further study the mechanisms for tumor promotion by p27 inactivation.
Finally, we analyzed the impact that a possible senescent checkpoint might have in the tumor promotion inhibition observed, crossing these lines to mammary specific p53(R172H) mutant expression, and to p27 knock-out mice.
The expression of SKP2, p27 and phospho-MAPK/ERK1/2 were strongly associated with cervical neoplastic progression (P<0.0001, P=0.006, P=0.003, respectively; Fisher's Exact Test).
In addition to enhanced p27 degradation, the possible other mechanisms which underlie its pathological functions in human cancer progression are also discussed.
There are conflicting data regarding the rate of its gene inactivation, the role of transcriptional and post-transcriptional factors, as well as its relationship to tumour progression and to the potential downstream regulator, the cell-cycle inhibitor p27.
These findings suggest that the target substrate of Skp2 in early esophageal SCC is mainly p27, and that failure of Skp2-induced degradation of p27 may influence tumor progression and lead to a poor prognosis.
Loss of p27 has not been significantly correlated with tumor proliferation in a number of studies and may reflect alterations in differentiation and adhesion-dependent growth regulation germane to oncogenesis and tumor progression.
Different studies have already shown that the isolated inactivation of p21, p16, or p27 cyclin-dependent kinase inhibitors (CKIs) is associated with increased growth fraction, tumor progression, or decreased overall survival in cases of non-Hodgkin's lymphoma.
Our findings suggest that the p27 109GG variant genotype may not play a major role in the etiology of SCCHN but may be associated with an increased risk in at-risk subgroups or subsets of SCCHN, particularly oral cavity cancer and possibly tumor progression.