Genes Predictive of G1 arrest in Melanoma Cell Lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Carson Craig
PROVIDER: S-ECPF-GEOD-40047 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Transcriptional profiling of human melanoma cell lines to identify a G1 arrest signature
2012-08-14 | GSE40047 | GEO
Project description:Transcriptional profiling of human melanoma cell lines to identify a G1 arrest signature Percentage of cells that arrest in G1 after irradiation was used to identify genes predictive of response
2012-08-13 | E-GEOD-40047 | biostudies-arrayexpress
Project description:The radiation response of Epstein-Barr virus (EBV)-immortalised lymphoblastoid cell lines derive from Li-Fraumeni syndrome (LFS) and LFS-like individuals was investigated. Cells from all LFS and LFS-like cases showed an accumulation of p53 protein following 137Cs gamma-irradiation, which was associated with cell cycle arrest at the G1/S border. This response was indistinguishable from that seen in cells derived from normal individuals, and occurred in cases with missense mutations in the TP53 gene at codons 175, 180, 220 and 248 and also in two LFS-like individuals with no TP53 mutation. Previous studies using lymphocytes and fibroblasts from LFS individuals have demonstrated abnormal radiation responses in these cells. This suggest cell type specificity in the contribution of a mutant p53 protein to phenotype.
| S-EPMC2074690 | biostudies-other
Project description:Melanoma cell lines and normal human melanocytes (NHM) were assayed for p53-dependent G1 checkpoint response to ionizing radiation (IR)-induced DNA damage. Sixty-six percent of melanoma cell lines displayed a defective G1 checkpoint. Checkpoint function was correlated with sensitivity to IR with checkpoint-defective lines being radio-resistant. Microarray analysis identified 316 probes whose expression was correlated with G1 checkpoint function in melanoma lines (P≤0.007) including p53 transactivation targets CDKN1A, DDB2, and RRM2B. The 316 probe list predicted G1 checkpoint function of the melanoma lines with 86% accuracy using a binary analysis and 91% accuracy using a continuous analysis. When applied to microarray data from primary melanomas, the 316 probe list was prognostic of 4-yr distant metastasis-free survival. Thus, p53 function, radio-sensitivity, and metastatic spread may be estimated in melanomas from a signature of gene expression.
| S-EPMC3397470 | biostudies-literature
Project description:Plant-derived polyphenols are being tested as chemopreventive agents; some polyphenols arrest the cell cycle at G1 phase, whereas others inhibit cell cycle proliferation at G2/M phase. Therefore, polyphenols have been proposed to inhibit cell cycle progression at different phases via distinct mechanisms. Indeed, our previous studies showed that small structural differences in polyphenols cause large differences in their biological activities; however, the details of the structural properties causing G1 cell cycle arrest remain unknown. In this study, we prepared 27 polyphenols, including eight different scaffolds, to gain insight into the structural conditions that arrest the cell cycle at G1 phase in a quantitative structure-activity relationship study. We used cell cycle profiles to determine the biophores responsible for G1 cell cycle arrest and believe that the biophores identified in this study will help design polyphenols that cause G1 cell cycle arrest.
| S-EPMC3759946 | biostudies-literature
Project description:To investigate the effect of HBV on the proliferative ability of host cells and explore the potential mechanism.MTT, colony formation assay and tumourigenicity in nude mice were performed to investigate the effect of HBV on the proliferative capability of host cells. In order to explore the potential mechanism, cell cycle and apoptosis were analysed. The cell cycle genes controlling the G1/S phase transition were detected by immunohistochemistry, westernblot and RT-PCR.HepG2.2.15 cells showed decreased proliferation ability compared to HepG2 cells. G1 phase arrest was the main cause but was not associated with apoptosis. p53, p21 and total retinoblastoma (Rb) were determined to be up-regulated, whereas cyclinE was down-regulated at both the protein and mRNA levels in HepG2.2.15 cells. The phosphorylated Rb in HepG2.2.15 cells was decreased.Our results suggested that HBV inhibited the capability of proliferation of HepG2.2.15 cells by regulating cell cycle genes expression and inducing G1 arrest.
| S-EPMC3104952 | biostudies-literature
Project description:BackgroundPterostilbene (PTER) is a dimethylated analog of the phenolic phytoalexin, resveratrol, with higher anticancer activity in various tumors. Herein, the molecular mechanisms by which PTER exerts its anticancer effects against acute myeloid leukemia (AML) cells were investigated.Methodology and principal findingsResults showed that PTER suppressed cell proliferation in various AML cell lines. PTER-induced G0/G1-phase arrest occurred when expressions of cyclin D3 and cyclin-dependent kinase (CDK)2/6 were inhibited. PTER-induced cell apoptosis occurred through activation of caspases-8-9/-3, and a mitochondrial membrane permeabilization (MMP)-dependent pathway. Moreover, treatment of HL-60 cells with PTER induced sustained activation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK)1/2, and inhibition of both MAPKs by their specific inhibitors significantly abolished the PTER-induced activation of caspases-8/-9/-3. Of note, PTER-induced cell growth inhibition was only partially reversed by the caspase-3-specific inhibitor, Z-DEVE-FMK, suggesting that this compound may also act through a caspase-independent pathway. Interestingly, we also found that PTER promoted disruption of lysosomal membrane permeabilization (LMP) and release of activated cathepsin B.ConclusionTaken together, our results suggest that PTER induced HL-60 cell death via MAPKs-mediated mitochondria apoptosis pathway and loss of LMP might be another cause for cell apoptosis induced by PTER.
| S-EPMC4140770 | biostudies-literature
Project description:BACKGROUND:Quinacrine (QC) is popular for its anti-malarial activity. It has been reported exhibiting anti-cancerous properties by suppressing nuclear factor-κB and activating p53 signaling; however, its effect on cellular pathways in human non-small cell lung cancer (NSCLC) has not been studied. MATERIALS AND METHODS:Binding of QC with GSTA1 was studied computationally as well as through GST activity assay kit. Cell viability, cell cycle and mitochondrial membrane potential activity were studied using flow cytometry. RT-PCR and western blot were carried out to understand the involvement of various genes at their mRNA as well as protein level. RESULTS:QC inhibited the activity of GSTA1 approximately by 40-45% which inhibits cell survival and promotes apoptosis. QC reduced viability of NSCLC cells in a dose-dependent manner. It also causes nuclear fragmentation, G1/S arrest of cell cycle and ROS generation; which along with disruption of mitochondrial membrane potential activity leads to apoptotic fate. CONCLUSIONS:Results revealed, QC has promising anti-cancer potential against NSCLC cells via inhibition of GSTA1, induction of G1/S arrest and ROS mediated apoptotic signaling.
| S-EPMC7210017 | biostudies-literature
Project description:Both preclinical and epidemiology studies associate ?-adrenoceptors-blockers (?-blockers) with activity against melanoma. However, the underlying mechanism is still unclear, especially in acral melanoma. In this study, we explored the effect of propranolol, a non-selective ?-blocker, on the A375 melanoma cell line, two primary acral melanoma cell lines (P-3, P-6) and mice xenografts. Cell viability assay demonstrated that 50?M-400?M of propranolol inhibited viability in a concentration and time dependent manner with an IC50 ranging from 65.33?M to 148.60?M for 24h -72h treatment, but propranolol (less than 200?M) had no effect on HaCaT cell line. Western blots showed 100?M propranolol significantly reduced the expression of Bcl-2 while increasing the expressions of Bax, cytochrome c, cleaved capase-9 and cleaved caspase-3, and down-regulated the levels of p-AKT, p-BRAF, p-MEK1/2 and p-ERK1/2 in melanoma cells, after a 24h incubation. The in vivo data confirmed the isolation results. Mice received daily ip. administration of propranolol at the dose of 2 mg/kg for 3 weeks and the control group was treated with the same volume of saline. The mean tumor volume at day 21 in A375 xenografts was 82.33 ± 3.75mm3vs. 2044.67 ± 54.57mm3 for the propranolol-treated mice and the control group, respectively, and 31.66 ± 4.67 mm3vs. 1074.67 ± 32.17 mm3 for the P-3 xenografts. Propranolol also reduced Ki67, inhibited phosphorylation of AKT, BRAF, MEK1/2 and ERK1/2 in xenografts. These are the first data to demonstrate that propranolol might inhibit melanoma by activating the intrinsic apoptosis pathway and inactivating the MAPK and AKT pathways.
| S-EPMC5356557 | biostudies-literature
Project description:Gene expression analyses of 1300 genes involved in UPS-signalling in malignant and non-malignant cells Gene ratio of references (non-malignant) were compared to gene ratio of samples (malignant cells) under non-treated conditions
| S-ECPF-GEOD-44973 | biostudies-other