This causes sequentially hyperplasia, dysplasia and well differentiates squamous cell carcinoma (SCC) with up-regulation of molecular markers like mutant-p53, Caspase-3 and caspase-9 and cyclin-D1.
To evaluate cyclin D1 overexpression in oral squamous cell carcinomas and adjacent non-tumour epithelium as a biomarker of premalignant fields and a risk factor for multiple tumour development.
Starting with the physiological regulation of cyclin D1, there is an evaluation of its functions, overexpression mechanisms, and the implications of the oncogenic activation of CCND1/cyclin D1 in oral squamous cell carcinoma.
In contrast, knocking down of CREPT in OSCC cell lines significantly reduced proliferation, colony formation and migration as well as the expression of cyclin D1 and c-Myc, but promoted apoptosis.
Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas.
Overexpression of β-catenin and cyclin D1 was significantly associated with poor overall survival (p = 0.003 and p = 0.0009, respectively; log rank test) in squamous cell carcinomas, not in adenocarcinomas.
Expression and inactivation of glycogen synthase kinase 3 alpha/ beta and their association with the expression of cyclin D1 and p53 in oral squamous cell carcinoma progression.
In addition, CCND1 overexpression was significantly related to PTEN promoter hypermethylation in the whole group and in the group of patients with squamous cell carcinoma and lymph node invasion.
A multivariable co-alteration analysis established 2 SCC subgroups: (i) patients in whom TP53 and cyclin pathway (CDKN2A and CCND1) alterations strongly correlated but in whom PIK3CA aberrations were less frequent; and (ii) patients with PIK3CA alterations in whom TP53 mutations were less frequent (all P ≤ 0 .001, multivariable analysis).
The high expression of TC1 (C8orf4) was correlated with the expression of β-catenin and cyclin D1 and the progression of squamous cell carcinomas of the tongue.
Our findings indicated that cyclin D1 expression correlates with detrimental clinicopathological outcome and poor prognosis in oral squamous cell carcinoma.
Knock down of PSPH dramatically diminished SCC cell proliferation and cyclin D1 levels in the presence of exogenous of l-serine production suggesting a non-canonical role for PSPH in epithelial carcinogenesis.