Please use this identifier to cite or link to this item:
https://doi.org/10.1172/JCI87583
DC Field | Value | |
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dc.title | Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma | |
dc.contributor.author | Kent, L.N | |
dc.contributor.author | Bae, S | |
dc.contributor.author | Tsai, S.-Y | |
dc.contributor.author | Tang, X | |
dc.contributor.author | Srivastava, A | |
dc.contributor.author | Koivisto, C | |
dc.contributor.author | Martin, C.K | |
dc.contributor.author | Ridolfi, E | |
dc.contributor.author | Miller, G.C | |
dc.contributor.author | Zorko, S.M | |
dc.contributor.author | Plevris, E | |
dc.contributor.author | Hadjiyannis, Y | |
dc.contributor.author | Perez, M | |
dc.contributor.author | Nolan, E | |
dc.contributor.author | Kladney, R | |
dc.contributor.author | Westendorp, B | |
dc.contributor.author | De Bruin, A | |
dc.contributor.author | Fernandez, S | |
dc.contributor.author | Rosol, T.J | |
dc.contributor.author | Pohar, K.S | |
dc.contributor.author | Pipas, J.M | |
dc.contributor.author | Leone, G | |
dc.date.accessioned | 2020-10-23T02:33:05Z | |
dc.date.available | 2020-10-23T02:33:05Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Kent, L.N, Bae, S, Tsai, S.-Y, Tang, X, Srivastava, A, Koivisto, C, Martin, C.K, Ridolfi, E, Miller, G.C, Zorko, S.M, Plevris, E, Hadjiyannis, Y, Perez, M, Nolan, E, Kladney, R, Westendorp, B, De Bruin, A, Fernandez, S, Rosol, T.J, Pohar, K.S, Pipas, J.M, Leone, G (2017). Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma. Journal of Clinical Investigation 127 (3) : 830-842. ScholarBank@NUS Repository. https://doi.org/10.1172/JCI87583 | |
dc.identifier.issn | 00219738 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/179227 | |
dc.description.abstract | Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss-and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1-and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer. | |
dc.publisher | American Society for Clinical Investigation | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | transcription factor E2F1 | |
dc.subject | transcription factor E2F3 | |
dc.subject | transcriptome | |
dc.subject | E2f1 protein, mouse | |
dc.subject | E2f3 protein, mouse | |
dc.subject | transcription factor E2F1 | |
dc.subject | transcription factor E2F3 | |
dc.subject | tumor protein | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | Article | |
dc.subject | cancer incidence | |
dc.subject | cancer prognosis | |
dc.subject | cancer survival | |
dc.subject | chromatin | |
dc.subject | chromatin immunoprecipitation | |
dc.subject | controlled study | |
dc.subject | copy number variation | |
dc.subject | disease course | |
dc.subject | DNA microarray | |
dc.subject | e2f1 gene | |
dc.subject | e2f3 gene | |
dc.subject | epigenetics | |
dc.subject | female | |
dc.subject | gain of function mutation | |
dc.subject | gene | |
dc.subject | gene dosage | |
dc.subject | gene expression | |
dc.subject | gene locus | |
dc.subject | gene mapping | |
dc.subject | gene mutation | |
dc.subject | genetic gain | |
dc.subject | genetic transcription | |
dc.subject | genetic variability | |
dc.subject | histopathology | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | immunoblotting | |
dc.subject | immunohistochemistry | |
dc.subject | liver cell carcinoma | |
dc.subject | male | |
dc.subject | mouse | |
dc.subject | mutation rate | |
dc.subject | nonhuman | |
dc.subject | polymerase chain reaction | |
dc.subject | protein expression | |
dc.subject | tumor volume | |
dc.subject | animal | |
dc.subject | genetics | |
dc.subject | knockout mouse | |
dc.subject | liver tumor | |
dc.subject | metabolism | |
dc.subject | tumor gene | |
dc.subject | Animals | |
dc.subject | Carcinoma, Hepatocellular | |
dc.subject | E2F1 Transcription Factor | |
dc.subject | E2F3 Transcription Factor | |
dc.subject | Gene Dosage | |
dc.subject | Genes, Neoplasm | |
dc.subject | Humans | |
dc.subject | Liver Neoplasms | |
dc.subject | Mice | |
dc.subject | Mice, Knockout | |
dc.subject | Neoplasm Proteins | |
dc.type | Article | |
dc.contributor.department | PHYSIOLOGY | |
dc.description.doi | 10.1172/JCI87583 | |
dc.description.sourcetitle | Journal of Clinical Investigation | |
dc.description.volume | 127 | |
dc.description.issue | 3 | |
dc.description.page | 830-842 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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