ArticleProceedings of the National Academy of Sciences of the United States of America2013
Evidence that Igf2 down-regulation in postnatal tissues and up-regulation in malignancies is driven by transcription factor E2f3.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 48 citations in OpenAlex.
- Leveraging IGF signaling to improve the spatial organization and regenerative potential of iPSC-derived vascularized liver organoids.Science advances · 2026Article
- IGF-mediated glucose signalling is retained in adult naked mole-rats.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026Article
- Maternal Obesity Leads to Muscle Dysfunction via H19-Mediated Programming of Insulin-Like Growth Factor 2 Signaling.Diabetes · 2026Article
- Insulin-Like Growth Factor 2 Reverses Synaptic and Cognitive Deficits in Fetal Growth Restriction Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Skeletal stem/progenitor cell-derived rather than osteoblast-derived IGF2 supports the development and homeostasis of skeletal system via STAT3.International journal of biological sciences · 2025Article
- Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy.Neuro-oncology · 2024Article
- Hypoxia impairs blood glucose homeostasis in naked mole-rat adult subordinates but not queens.The Journal of experimental biology · 2024Article
- Human IGF2 Gene Epigenetic and Transcriptional Regulation: At the Core of Developmental Growth and Tumorigenic Behavior.Biomedicines · 2023Review
- IGF2 in memory, neurodevelopmental disorders, and neurodegenerative diseases.Trends in neurosciences · 2023Review
- Insulin-like Growth Factor-2 (IGF-2) in Fibrosis.Biomolecules · 2022Review
- Review
- Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear.Scientific reports · 2021Article
- Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand.Scientific reports · 2021Article
- Modulation of IGF2 Expression in the Murine Thymus and Thymic Epithelial Cells Following Coxsackievirus-B4 Infection.Microorganisms · 2021Article
- Review
- Critical role of SOX2-IGF2 signaling in aggressiveness of bladder cancer.Scientific reports · 2020Article
- Focal Adhesion Kinase and β-Catenin Cooperate to Induce Hepatocellular Carcinoma.Hepatology (Baltimore, Md.) · 2019Article
- Genome-wide association analysis for body weight identifies candidate genes related to development and metabolism in rainbow trout (Oncorhynchus mykiss).Molecular genetics and genomics : MGG · 2019Article
- Cartilage-Targeted IGF-1 Treatment to Promote Longitudinal Bone Growth.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions.PLoS biology · 2018Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Insulin-like growth factor 2 (IGF2) is an important fetal growth factor. Its expression is dramatically down-regulated in multiple organs after birth but is frequently up-regulated in cancers. The mechanisms that drive down-regulation of IGF2 in postnatal tissues or the up-regulation in malignancy are unclear. We found evidence that E2F transcription factor 3 (E2F3) drives these changes in expression. E2f3 mRNA expression, protein expression, and binding to the Igf2 promoter all decreased with age postnatally in multiple mouse organs. In late juvenile hepatocytes, restoration of high E2f3 expression restored high Igf2 expression, indicating a causal relationship, but this induction did not occur in fetal hepatocytes, which already have high E2f3 and Igf2 expression. Transient expression of E2f3 in both HEK293 cells and in late juvenile hepatocytes were able to activate reporter constructs containing the mouse Igf2 promoter P2, which includes consensus E2F-binding sites. In humans, microarray data revealed declines in E2F3 and IGF2 expression with age similar to the mouse. In addition, E2F3-overexpressing human prostate and bladder cancers showed increased IGF2 expression, and levels of E2F3 and IGF2 mRNA in these cancers were positively correlated. Taken together, the findings suggest that down-regulation of E2f3 with age helps drive the dramatic decline in Igf2 expression in postnatal organs, and E2F3 overexpression in human cancers induces IGF2 overexpression.
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