Cited by 386Protein Kinase Regulation and GTPase SignalingCarcinogens and Genotoxicity AssessmentMelanoma and MAPK Pathways

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Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells.

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Dong, Z, Birrer, M J, Watts, R G, Matrisian, L M, Colburn, N H·1994·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.91.2.609PMC PMC42998

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Abstract

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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Additional file 4 of CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
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Additional file 2 of CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
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Additional file 6 of CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
Zhang, X., Guo, Y., Xiao, T., Li, J., Guo, A., Lei, L., Jin, C., Long, Q., Su, J., Yin, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20486675
Additional file 3 of CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
Zhang, X., Guo, Y., Xiao, T., Li, J., Guo, A., Lei, L., Jin, C., Long, Q., Su, J., Yin, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20486666
Additional file 1 of CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
Zhang, X., Guo, Y., Xiao, T., Li, J., Guo, A., Lei, L., Jin, C., Long, Q., Su, J., Yin, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20486660
Additional file 5 of CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
Zhang, X., Guo, Y., Xiao, T., Li, J., Guo, A., Lei, L., Jin, C., Long, Q., Su, J., Yin, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20486672
Efficiency of all-trans retinoic acid on gastric cancer
Hajipour, M., Mokhtari, K., & Peymani, M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-22305-1.00015-1
p16INK4a, régulation du cycle cellulaire et microARN
Chien, W. W. (2009) · theses.fr (ABES) · doi:10.70675/dbb5386dzc679z454fzad91z9d53a61231ff
BindingDB Entry 50033843: Grassypeptolides F and G, cyanobacterial peptides from Lyngbya majuscula.
BindingDB (2012) · UC San Diego · doi:10.7270/q2gm87p2
BindingDB Entry 50033659: Nothospondin, a new AP-1 inhibitory quassinoid from the Cameroonian plant Nothospondias staudtii.
BindingDB (2012) · UC San Diego · doi:10.7270/q2zk5h1q
Studies on tumor promotion and progression: The importance of signaling by activator protein-1 and prostaglandin E₂
Thompson, E. J. (2002) · UA Campus Repository (The University of Arizona)

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.
ORCID: Dong, Z
Birrer, M J
Matrisian, L M
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
DOI: 10.1073/pnas.91.2.609
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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Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells.

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