Alterations of the Retinoblastoma (Rb) pathway are frequent in ovarian cancer, typically resulting from <i>CDKN2A</i> down-regulation, <i>CCNE1</i> amplification, <i>CCND1/2</i> amplification, and <i>RB1</i> loss.
SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16<sup>INK4a</sup>-deficient profile associated with positive responses to CDK4/6 inhibitors.
Flow cytometry assay then determined that TCF over-expression helps HCC cell G1/S phase transition, and further research showed that TCF19 up-regulation inhibits p57Kip2, p21Cip1 and p27Kip1 cell cycle suppressors, enhances the expression of cyclin D1 expression and simulates retinoblastoma (Rb), FOXO1 and AKT phosphorylation.
Ribociclib is a specific cyclin dependent kinase (Cdk) 4/6 inhibitor that induces G<sub>1</sub> arrest by blocking the formation of cyclin D1-Cdk4/6 complex and inhibiting retinoblastoma (RB) phosphorylation.
The combinatory treatment cooperatively demonstrated more complete inhibition of Rb phosphorylation, and LY3009120 suppressed the cyclin D1 upregulation mediated by abemaciclib.
The levels of cyclin D1 and cyclin E1 and phospho-retinoblastoma, which are known to promote the cell cycle progression from G0 or G1 into S phase, were decreased in CEMIP-silenced cells.
Cyclin D1 and p27<sup>Kip1</sup> regulate the activity of cyclin D1-CDK4 complexes and retinoblastoma (Rb), and then they stimulate the progression of G1/S transition and tumour cell proliferation.
Immunoprecipitation assay and ChIP-quantitative PCR results showed that FGF9-induced Rb phosphorylation led to the dissociation of Rb-E2F1 complexes and thereby enhanced the transactivations of E2F1 target genes, Cyclin D1, Cyclin E1 and Cyclin A1.
We further demonstrated that ABT-263 treatment markedly increased the expression of p21<sup>Waf1/Cip1</sup> and decreased the expression of cyclin D1 and phospho-Rb (retinoblastoma tumor suppressor protein) (Ser780) proteins that contributed to the G<sub>1</sub>/G<sub>0</sub>-phase arrest.
In skin and tumour biopsies, dinaciclib reduced Rb phosphorylation at CDK2 phospho-sites and modulated expression of cyclin D1 and p53, suggestive of CDK9 inhibition.
We find that stoichiometric inhibition of cyclin D1-CDK4 activity by p21 controls the retinoblastoma (Rb) and E2F transcription program in an ultrasensitive manner.
Similarly, BD0801 decreased AKT, Erk1/2, and Rb phosphorylation and cyclin D1 expression whereas it increased p21 protein expression in mouse HCC tumor xenografts.
Nevertheless, when clustering analysis was performed, patients with tumors featuring low levels of p16, cyclin D1 and p53 with concomitantly high levels of pRB had reduced risk for relapse (Wald's p=0.015).
Mechanistically, ribavirin inhibited eIF4E function in retinoblastoma cells as shown by the decreased protein levels of Cyclin D1, c-Myc and VEGF without affecting their mRNA expression.
Following further examination of cell cycle-related factors, MCM2 knockdown inhibited protein retinoblastoma (Rb), cyclin D1 and CDK4 expression, but increased p21 and p53 expression, suggesting that siMCM2 indeed triggered cell cycle arrest.In addition, siMCM2 induced apoptosis.
Quantitative multi-gene fluorescence in situ hybridization was used to study CNAs of the genes involved in the G1/S checkpoint signaling pathway, including cyclin d1 (CCND1), c-Myc, p21, cell-cycle-checkpoint kinase 2 gene, p16, retinoblastoma (Rb1), murine double minute 2 (Mdm2) and p53, in 60 TNBC samples and 60 non-TNBC samples.
On the other hand, knockdown of p16(ink4a) sensitizes cancer cells to TSC2 knockdown induced cell death in a manner that is likely dependant on serum induction of Cyclin D1 to inactivate the Rb function.
UV-C, as well as EGFR kinase inhibitors, decreased the expression level of cyclin D1 and the phosphorylated level of retinoblastoma, indicating that EGFR down-regulation is correlated to cell cycle arrest.
These findings reveal an unexpected function of a core cell cycle protein in DNA repair and suggest that targeting cyclin D1 may be beneficial also in retinoblastoma-negative cancers which are currently thought to be unaffected by cyclin D1 inhibition.
The protein and mRNA expressions of cyclin D1, proliferating cell nuclear antigen (PCNA), retinoblastoma (Rb), and p16 were observed with immunofluorescence and RT-PCR, respectively.