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Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells.
Open accessAbstract
AP-1 transcriptional activity is stimulated by the transformation promoters phorbol 12-myristate 13-acetate ("12-O-tetradecanoylphorbol 13-acetate," TPA) and epidermal growth factor (EGF) in promotion-sensitive (P+) but not in promotion-resistant (P-) JB6 mouse epidermal cell lines. Although TPA stimulates expression of the jun and fos family genes, only c-jun expression shows higher elevation in P+ cells than in P- cells. The present study tests the hypothesis that induced AP-1 activity is required for tumor promoter-induced transformation in JB6 P+ cells. Both retinoic acid and the glucocorticoid fluocinolone acetonide inhibited basal and TPA-induced AP-1 activities that were tested with a stromelysin promoter-chloramphenicol acetyltransferase reporter gene in P+ cells. Since both retinoic acid and fluocinolone acetonide are active in inhibiting TPA-induced anchorage-independent transformation of P+ cells in the dose range that blocks TPA-induced AP-1 activity, their antipromoting effects may occur through inhibition of AP-1 activity. To test the hypothesis with a more specific inhibitor, stable clonal transfectants of P+ cells expressing dominant negative c-jun mutant encoding a transcriptionally inactive product were analyzed. All transfectants showed a block in TPA and EGF induction of AP-1 activity. All transfectants also showed inhibition of TPA-induced transformation, and most transfectants showed a block in EGF-induced transformation. These results indicate that AP-1 activity is required for TPA- or EGF-induced transformation. This work demonstrates that a specific block in induced AP-1 activity inhibits tumor promoter-induced transformation.
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“Activation protein-1 (AP-1), a trans-acting transcription factor, was shown to be stimulated in the promotion sensitive (P+), but not in the promotion resistant (P-) cells [4,5].”
From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [4]
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Nomura, M., Kaji, A., Ma, W., Miyamoto, K., & Dong, Z. (2001) · Molecular Carcinogenesis · doi:10.1002/mc.1043 · Cited by 84
Self-citationChoi, B. Y., Choi, H. S., Ko, K., Cho, Y., Zhu, F., Kang, B. S., Ermakova, S. P., Ma, W., Bode, A. M., & Dong, Z. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb960 · Cited by 83
Self-citationSkin Cancer Chemoprevention: Strategies to Save Our Skin
Einspahr, J. G., Bowden, G. T., & Alberts, D. S. (2003) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-642-55647-0_14 · Cited by 83
Metadata
- Authors
- Dong, Z., Birrer, M. J., Watts, R. G., Matrisian, L. M., & Colburn, N. H.
- Affiliations
- Biological Carcinogenesis and Development Program, PRI/DynCorp, Frederick, MD.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-01-18
- Volume
- 91
- Issue
- 2
- Pages
- 609-613
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC42998
- OpenAlex
- W2009379675
- Cited by
- 386
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 6 · 2014: 7 · 2013: 9 · 2012: 12
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- AP-1 transcription factor, tumor promotion, JB6 epidermal cells, phorbol myristate acetate, epidermal growth factor, c-Jun, retinoic acid, fluocinolone acetonide
- MeSH terms
- Animals, Base Sequence, Binding Sites, Cell Line, Cell Transformation, Neoplastic, DNA, Epidermal Growth Factor, Fluocinolone Acetonide, Molecular Sequence Data, Skin, Tetradecanoylphorbol Acetate, Transfection, Tretinoin, Gene Expression, Mutagenesis, Site-Directed, Proto-Oncogene Proteins c-jun, Genes, jun, Genes, fos, Point Mutation, Genes, Reporter, Mice
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