The decreased proliferation rate was accompanied by an upregulation of P53 and Retinoblastoma mRNA and a downregulation of c-Myc and hTERT mRNA levels.
AT‑101 markedly downregulated the protein levels of phospho‑retinoblastoma (Ser 780) and cyclin D1, whereas it elevated protein levels of p53 and p21Waf1/Cip1, contributing to the inhibition of cell cycle progression.
Head and neck HPV-NEC is a rare, aggressive entity that can show mixed small and large cell features and p16 upregulation; p53 and Rb are variable with limited diagnostic utility.
In summary, the TFF3 signaling pathway in Y79 RB cells involves the activation of p53 with downstream induction of miR-34a and subsequent inhibition of EMP1.
On the other hand, HLP-mediated cell cycle G0/G1 arrest might be exerted by inducing the expressions of p53 and its downstream factors that, in turn, suppress cyclin E/cdk2 activity, preventing retinoblastoma (Rb) phosphorylation and the subsequent dissociation of Rb/E2F complex.
Specifically, targeting cellular pathways frequently altered in glioblastoma, such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), the p53 and the retinoblastoma (RB) pathways, or epidermal growth factor receptor (EGFR) gene amplification or mutation, have failed to improve outcome, likely because of redundant compensatory mechanisms, insufficient target coverage related in part to the blood brain barrier, or poor tolerability and safety.
When hr-HPV integrates into the host genome, the constitutive expression of oncogenic HPV proteins E6 and E7 function to disrupt p53 and retinoblastoma regulation of cell cycle, respectively, to favor malignant transformation.
Clinicopathologic and genomic characterizations of CRPC tumors lead to subdividing CRPC into two subtypes: (1) AR-dependent CRPC containing dysregulation of AR signaling alterations in AR such as amplification, point mutations, and/or generation of splice variants in the AR gene; and (2) an aggressive variant PCa (AVPC) subtype that is phenotypically similar to small cell prostate cancer and is defined by chemotherapy sensitivity, gain of neuroendocrine or pro-neural marker expression, loss of AR expression, and combined alterations of PTEN, TP53, and RB1 tumor suppressors.
Single-cell RNA profiles of PNECs are heterogeneous; when RB levels are reduced, the profiles resemble those from early-stage SCLC; and when both RB and TP53 levels are reduced, the transcriptome is enriched with cell cycle-specific RNAs.
Our findings demonstrate that Ziyu I exhibits excellent anticancer effect on human RB WERI-Rb-1 cells by triggering p53 activation, and imply Ziyu I as a potential compound for chemotherapy of human RB.
The inactivation of both TP53 and of the retinoblastoma (pRb) tumor suppressors, as induced by the viral oncogenes large and small T of SV40, triggers anchorage-independent growth in RAS, HDAC4-TM and, to a lesser extent, in HDAC4-wild type (WT)-expressing cells.
PD0332991 also inhibited CDK6‑specific phosphorylation of retinoblastoma on Ser780, reduced the expression of cyclin D1, and induced expression of p53 and p27.
Following infection of HMECs with HCMV-DB, we observed the inactivation of retinoblastoma and p53 proteins, the activation of telomerase activity, the activation of the proto-oncogenes c-Myc and Ras, the activation of Akt and STAT3, and the upregulation of cyclin D1 and Ki67 antigen.
Genomic studies have established a set of three core-signaling pathways, receptor tyrosine kinase (RTK), p53 and retinoblastoma (Rb) signaling pathways, contributing glioblastoma (GBM) and revealed that dysregulation of at least two pathways is required for GBM progression.
Cellular senescence represents a permanent withdraw from cell cycle in response to diverse stress; it is controlled by the p53 and retinoblastoma protein (RB) tumor suppressors, and constitutes a potent anticancer mechanisms. p53 can be deacetylated by a protein complex containing histone deacetylases (HDAC1).
Inhibition of the interaction between p53 and HDM2 is an effective therapeutic strategy in cancers that harbor a wild-type p53 protein such as retinoblastoma (RB).
Western blot analysis demonstrated that arctigenin increased the expression levels of p21, retinoblastoma and p53 proteins, and significantly decreased the expression levels of cyclin D1 and cyclin-dependent kinase 4 proteins.
These findings indicate that high-level MDM2 expression is needed in order to perform a critical p53-independent function and may obviate the need for genomic alterations to the p53 pathway during retinoblastoma tumorigenesis.
These alterations affecting the MAP kinase, PI3K/Akt, Wnt, IDH (metabolic) and Tp53/Rb1 signaling pathways may provide the opportunity for defining targeted therapeutic approaches.