Dataset Information

Reduced eukaryotic initiation factor 2Bepsilon-subunit expression suppresses the transformed phenotype of cells overexpressing the protein.

ABSTRACT: Eukaryotic initiation factor 2B (eIF2B), a five-subunit guanine nucleotide exchange factor, plays a key role in the regulation of mRNA translation. Expression of its epsilon-subunit is specifically up-regulated in certain conditions associated with increased cell growth. Therefore, the purpose of the present study was to examine the effect of repressing eIF2Bepsilon expression on growth rate, protein synthesis, and other characteristics of two tumorigenic cell lines that display up-regulated expression of the epsilon-subunit. Experiments were designed to compare spontaneously transformed fibroblasts to transformed mouse embryonic fibroblasts infected with a lentivirus containing a short hairpin RNA directed against eIF2Bepsilon. Cells expressing the short hairpin RNA displayed a reduction in eIF2Bepsilon abundance to 30% of the value observed in uninfected transformed mouse embryonic fibroblasts, with no change in the expression of any of the other four subunits. The repression of eIF2Bepsilon expression was accompanied by reductions in guanine nucleotide exchange factor activity and global rates of protein synthesis. Moreover, repressed eIF2Bepsilon expression led to marked reductions in cell growth rate in culture, colony formation in soft agar, and tumor progression in nude mice. Similar results were obtained in MCF-7 human breast cancer cells in which eIF2Bepsilon expression was repressed through transient transfection with a small interfering RNA directed against the epsilon-subunit. Overall, the results support a role for eIF2Bepsilon in the regulation of cell growth and suggest that it might represent a therapeutic target for the treatment of human cancer.

SUBMITTER: Gallagher JW

PROVIDER: S-EPMC2664734 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Reduced eukaryotic initiation factor 2Bepsilon-subunit expression suppresses the transformed phenotype of cells overexpressing the protein.

Gallagher James W JW Kubica Neil N Kimball Scot R SR Jefferson Leonard S LS

Cancer research 20081101 21

Eukaryotic initiation factor 2B (eIF2B), a five-subunit guanine nucleotide exchange factor, plays a key role in the regulation of mRNA translation. Expression of its epsilon-subunit is specifically up-regulated in certain conditions associated with increased cell growth. Therefore, the purpose of the present study was to examine the effect of repressing eIF2Bepsilon expression on growth rate, protein synthesis, and other characteristics of two tumorigenic cell lines that display up-regulated exp ...[more]

PMID: 18974117

Similar Datasets

Project description:Liver cancer is one of the major malignancies with the worst prognosis among all solid tumor types. It is therefore ponderable to explore prognostic biomarkers and therapeutic targets for liver cancer. Eukaryotic translation initiation factor 3 subunit B (EIF3B) is closely linked to the transcription initiation of cancer-associated genes. In the present study, EIF3B was indicated to be a potential prognostic biomarker of liver cancer. The mRNA expression level of EIF3B in liver cancer was assessed by analyzing the Cancer Genome Atlas dataset. ?2 and Fisher's exact tests were used to assess the association of EIF3B expression with clinical parameters. Receiver-operating characteristic curve analysis was used for evaluating the diagnostic value of EIF3B. Overall and relapse-free survival were assessed using Kaplan-Meier curves to determine the association between EIF3B expression and survival. Univariate and multivariate Cox regression analysis were performed to identify the factors affecting overall/relapse-free survival. Gene set enrichment analysis (GSEA) was used to identify signaling pathways associated with EIF3B in liver cancer. It was revealed that EIF3B was highly expressed in liver cancer tissues and it had a promising diagnostic ability. Furthermore, the survival analysis indicated that patients with high EIF3B expression generally had shorter overall as well as relapse-free survival. Univariate and multivariate Cox analysis suggested that high EIF3B mRNA expression may serve as an independent biomarker for the prognostication of patients with liver cancer. GSEA suggested that MYC-V1 (HALLMARK_MYC_TARGETS_V1 geneset; P=0.009), MYC-V2 (HALLMARK_MYC_TARGETS_V2 geneset; P=0.004) and DNA repair pathways (HALLMARK_DNA_REPAIR geneset; P<0.001) were differentially enriched in high EIF3B expression and low EIF3B expression groups. In conclusion, high EIF3B expression was indicated to be an independent prognostic biomarker for patients with liver cancer.

Dataset Information

Reduced eukaryotic initiation factor 2Bepsilon-subunit expression suppresses the transformed phenotype of cells overexpressing the protein.

Publications

Reduced eukaryotic initiation factor 2Bepsilon-subunit expression suppresses the transformed phenotype of cells overexpressing the protein.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets