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

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

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

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.

Integrity signals

Registry

Crossref · 10.1073/pnas.91.2.609

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • AP-1 is stimulated in promotion sensitive P+ JB6 cells but not in promotion resistant P- cells.

    “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].”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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
Published
1994-01-18
Volume
91
Issue
2
Pages
609-613
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review