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.
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.
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).
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.
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.
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.
In conclusion, MAGE-A3 may serve as a diagnostic and prognostic biomarker for patients with NSCLC, due to its association with tumor progression and poor clinical outcome.
A ZASC1 copy number that has increased from primary to recurrent tumor counterparts in tissue pairs suggested the importance of ZASC1 in tumor progression.
Multivariate Cox regression models revealed that hypermethylation of ZNF492 [hazard ratio (HR), 5.44; P=0.001] and GPR149 (HR, 7.07; P<0.001) may be independent predictors of tumor progression.
Besides these genetic lesions, only two point mutations that may affect tumour progression were identified: A frame-shift deletion in RNF146 and a missense mutation in a zinc finger of ZNF407.
Given these results it is possible that under hypoxic conditions, elevated levels of ZNF395 may support inflammation and cancer progression by activating the target genes involved in the innate immune response and cancer.
Moreover, an inverse correlation of expression levels was observed between ZBRK1 and KAP1 following tumor progression from in situ carcinoma to invasive/metastatic cervical cancer specimens.