ArticleOncogene2012
Established and new mouse models reveal E2f1 and Cdk2 dependency of retinoblastoma, and expose effective strategies to block tumor initiation.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- VEGF overexpression is associated with optic nerve involvement and differentiation of retinoblastoma: A PRISMA-compliant meta-analysis.Medicine · 2018Pooled it
- Abemaciclib Inhibits Retinoblastoma Tumor Growth by Targeting CDK1/2.Investigative ophthalmology & visual science · 2026Article
- Dedifferentiation-driven oncogenic stemness promotes tumor-sustaining adaptability in the intestinal epithelium.Cell death & disease · 2026Article
- The tumor suppressor pRb and its relative p130 are required to maintain murine adult skeletal muscle homeostasis.Oncogene · 2025Article
- The prognostic and neuroendocrine implications of SLC25A29-mediated biomass signature in prostate cancer.GeroScience · 2025Article
- Article
- Targeting GPC2 on Intraocular and CNS Metastatic Retinoblastomas with Local and Systemic Delivery of CAR T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Retinoblastoma: present scenario and future challenges.Cell communication and signaling : CCS · 2023Review
- Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers.Molecular cancer research : MCR · 2023Article
- Article
- E2F1 Expression and Apoptosis Initiation in Crayfish and Rat Peripheral Neurons and Glial Cells after Axonal Injury.International journal of molecular sciences · 2022Article
- InVision: An optimized tissue clearing approach for three-dimensional imaging and analysis of intact rodent eyes.iScience · 2021Article
- Article
- Single-Cell Analysis of Human Retina Identifies Evolutionarily Conserved and Species-Specific Mechanisms Controlling Development.Developmental cell · 2020Article
- Heavenly HELLS? A potential new therapeutic target for retinoblastoma.Oncoscience · 2020Article
- Preclinical studies reveal MLN4924 is a promising new retinoblastoma therapy.Cell death discovery · 2020Article
- The broken cycle: E2F dysfunction in cancer.Nature reviews. Cancer · 2019Review
- Developmental stage-specific proliferation and retinoblastoma genesis in RB-deficient human but not mouse cone precursors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Chromatin remodeling protein HELLS is upregulated by inactivation of the RB-E2F pathway and is nonessential for osteosarcoma tumorigenesis.Oncotarget · 2018Article
- Rb is required for retinal angiogenesis and lamination.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
RB(+/-) individuals develop retinoblastoma and, subsequently, many other tumors. The Rb relatives p107 and p130 protect the tumor-resistant Rb(-/-) mouse retina. Determining the mechanism underlying this tumor suppressor function may expose novel strategies to block Rb pathway cancers. p107/p130 are best known as E2f inhibitors, but here we implicate E2f-independent Cdk2 inhibition as the critical p107 tumor suppressor function in vivo. Like p107 loss, deleting p27 or inactivating its Cdk inhibitor (CKI) function (p27(CK-)) cooperated with Rb loss to induce retinoblastoma. Genetically, p107 behaved like a CKI because inactivating Rb and one allele each of p27 and p107 was tumorigenic. Although Rb loss induced canonical E2f targets, unexpectedly p107 loss did not further induce these genes, but instead caused post-transcriptional Skp2 induction and Cdk2 activation. Strikingly, Cdk2 activity correlated with tumor penetrance across all the retinoblastoma models. Therefore, Rb restrains E2f, but p107 inhibits cross talk to Cdk. While removing either E2f2 or E2f3 genes had little effect, removing only one E2f1 allele blocked tumorigenesis. More importantly, exposing retinoblastoma-prone fetuses to small molecule inhibitors of E2f (HLM006474) or Cdk (R547) for merely 1 week dramatically inhibited subsequent tumorigenesis in adult mice. Protection was achieved without disrupting normal proliferation. Thus, exquisite sensitivity of the cell-of-origin to E2f and Cdk activity can be exploited to prevent Rb pathway-induced cancer in vivo without perturbing normal cell division. These data suggest that E2f inhibitors, never before tested in vivo, or CKIs, largely disappointing as therapeutics, may be effective preventive agents.
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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.