ArticleProceedings of the National Academy of Sciences of the United States of America1999
Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 381 citations in OpenAlex.
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- The CaSR Modulator NPS-2143 Reduced UV-Induced DNA Damage in Skh:hr1 Hairless Mice but Minimally Inhibited Skin Tumours.International journal of molecular sciences · 2023Article
- The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review.International journal of molecular sciences · 2022Review
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- The Fra-1/AP-1 Oncoprotein: From the "Undruggable" Transcription Factor to Therapeutic Targeting.Cancers · 2022Review
- Signaling of MK2 sustains robust AP1 activity for triple negative breast cancer tumorigenesis through direct phosphorylation of JAB1.NPJ breast cancer · 2021Article
- Transcriptional and signalling regulation of skin epithelial stem cells in homeostasis, wounds and cancer.Experimental dermatology · 2021Review
- BACH2-mediated FOS confers cytarabine resistance via stromal microenvironment alterations in pediatric ALL.Cancer science · 2021Observational
- A Driver Never Works Alone-Interplay Networks of Mutant p53, MYC, RAS, and Other Universal Oncogenic Drivers in Human Cancer.Cancers · 2020Review
- Antiproliferative effects of the CDK6 inhibitor PD0332991 and its effect on signaling networks in gastric cancer cells.International journal of molecular medicine · 2018Article
- MAPK/c-Jun signaling pathway contributes to the upregulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL induced by Epstein-Barr virus-encodedOncology letters · 2018Article
- Embryonic AP1 Transcription Factor Deficiency Causes a Collodion Baby-Like Phenotype.The Journal of investigative dermatology · 2017Article
- The TLR4-NOS1-AP1 signaling axis regulates macrophage polarization.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- JunB promotes cell invasion, migration and distant metastasis of head and neck squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2016Article
- Interplay among Drosophila transcription factors Ets21c, Fos and Ftz-F1 drives JNK-mediated tumor malignancy.Disease models & mechanisms · 2015Article
- Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth.Nature cell biology · 2015Article
- Article
- Structural and biochemical changes underlying a keratoderma-like phenotype in mice lacking suprabasal AP1 transcription factor function.Cell death & disease · 2015Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
Activator protein-1 (AP-1) is a transcription factor that consists of either a Jun-Jun homodimer or a Jun-Fos heterodimer. Transactivation of AP-1 is required for tumor promoter-induced transformation in mouse epidermal JB6 cells and for progression in mouse and human keratinocytes. Until now, the question of whether AP-1 transactivation is required for carcinogenesis in vivo has remained unanswered, as has the issue of functionally significant target genes. To address these issues we have generated a transgenic mouse in which transactivation mutant c-jun (TAM67), under the control of the human keratin-14 promoter, is expressed specifically in the basal cells of the epidermis where tumor induction is initiated. The keratin-14-TAM67 transgene was expressed in the epidermis, tongue, and cervix, with no apparent abnormalities in any tissue or organ. TAM67 expression blocked 12-O-tetradecanoylphorbol 13-acetate (TPA, phorbol 12-tetradecanoate 13-acetate) induction of the AP-1-regulated luciferase in AP-1 luciferase/TAM67 mice, but did not inhibit induction of candidate AP-1 target genes, collagenase-1 or stromelysin-3. More interestingly, TAM67 expression did not inhibit TPA-induced hyperproliferation. In two-stage skin carcinogenesis experiments, the transgenic animals showed a dramatic inhibition of papilloma induction. We conclude that transactivation of a subset of AP-1-dependent genes is required for tumor promotion and may be targeted for cancer prevention.
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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.