ArticleCancer cell international2003
Expression of constitutively active 4EBP-1 enhances p27Kip1 expression and inhibits proliferation of MCF7 breast cancer cells.
Article in Cancer cell international, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 56 citations in OpenAlex.
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- eIF4E-independent translation is largely eIF3d-dependent.Nature communications · 2024Article
- Chalcone-3 Inhibits the Proliferation of Human Breast Cancer MDA-MB-231 Cell Line.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Cell cycle control by the insulin-like growth factor signal: at the crossroad between cell growth and mitotic regulation.Cell cycle (Georgetown, Tex.) · 2023Review
- The consequences of increased 4E-BP1 in polycystic kidney disease.Human molecular genetics · 2019Article
- Therapeutic Opportunities in Eukaryotic Translation.Cold Spring Harbor perspectives in biology · 2018Review
- Developing anti-neoplastic biotherapeutics against eIF4F.Cellular and molecular life sciences : CMLS · 2017Review
- Role of Eukaryotic Initiation Factors during Cellular Stress and Cancer Progression.Journal of nucleic acids · 2016Review
- Rapamycin-induced G1 cell cycle arrest employs both TGF-β and Rb pathways.Cancer letters · 2015Article
- Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.International journal of molecular sciences · 2013Article
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- Eukaryotic translation initiation factor 4E binding protein 1 (4EBP-1) function is suppressed by Src and protein phosphatase 2A (PP2A) on extracellular matrix.The Journal of biological chemistry · 2011Article
- Mammalian target of rapamycin: a central node of complex signaling cascades.International journal of clinical and experimental pathology · 2011Review
- An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1.The Journal of biological chemistry · 2009Article
- Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1.Oncogene · 2008Article
- Rapamycin inhibits multiple stages of c-Neu/ErbB2 induced tumor progression in a transgenic mouse model of HER2-positive breast cancer.Molecular cancer therapeutics · 2007Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEukaryotic initiation factor 4E (eIF4E) is essential for cap-dependent initiation of translation. Cell proliferation is associated with increased activity of eIF4E and elevated expression of eIF4E leads to tumorigenic transformation. Many tumors express very high levels of eIF4E and this may be a critical factor in progression of the disease. In contrast, overexpression of 4EBP, an inhibitor of eIF4E, leads to cell cycle arrest and phenotypic reversion of some transformed cells.
resultsA constitutively active form of 4EBP-1 was inducibly expressed in the human breast cancer cell line MCF7. Induction of constitutively active 4EBP-1 led to cell cycle arrest. This was not associated with a general inhibition of protein synthesis but rather with changes in specific cell cycle regulatory proteins. Cyclin D1 was downregulated while levels of the CDK inhibitor p27Kip1 were increased. The levels of cyclin E and CDK2 were unaffected but the activity of CDK2 was significantly reduced due to increased association with p27Kip1. The increase in p27Kip1 did not reflect changes in p27Kip1 mRNA or degradation rates. Rather, it was associated with enhanced synthesis of the protein, even though 4EBP-1 is expected to inhibit translation. This could be explained, at least in part, by the ability of the p27Kip1 5'-UTR to mediate cap-independent translation, which was also enhanced by expression of constitutively active 4EBP-1.
conclusionsExpression of active 4EBP-1 in MCF7 leads to cell cycle arrest which is associated with downregulation of cyclin D1 and upregulation of p27Kip1. Upregulation of p27Kip1reflects increased synthesis which corresponds to enhanced cap-independent translation through the 5'-UTR of the p27Kip1 mRNA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.