Cited by 160Cancer-related Molecular PathwaysMechanisms of cancer metastasisProtein Kinase Regulation and GTPase Signaling

Pdcd4 suppresses tumor phenotype in JB6 cells by inhibiting AP-1 transactivation

Yang, Hsin-Sheng, Knies, Jennifer L, Stark, Cristi, Colburn, Nancy H·2003·Oncogene

Abstract

Transformation suppressor Pdcd4 is downregulated in transformed (Tx) mouse epidermal JB6 RT101 cells relative to transformation-resistant (P-) and susceptible (P+) variants. Whether Pdcd4 downregulation is necessary not only to induce transformation but also to maintain tumor phenotypes has not been determined previously. In the present study, overexpression of Pdcd4 cDNA in stably transfected RT101 cells resulted in 40% fewer anchorage-independent colonies that were smaller in size than the vector control colonies, indicating that elevated Pdcd4 expression is sufficient to suppress tumor phenotype. Transient transfection of Pdcd4 expression plasmid and 4 x AP-1 reporter gene showed that activation of AP-1-dependent transcription was inhibited by Pdcd4 expression in a concentration-dependent manner. In contrast, Pdcd4 did not inhibit serum response element-dependent transcription, indicating specificity. In a Gal4 fusion assay, Pdcd4 specifically inhibited activation of c-Jun and c-Fos activation domains, but did not inhibit activation of JunB, JunD, Fra-1, or Fra-2. Gel mobility shift assay demonstrated that c-Jun is the major component detected in the AP-1 complex in RT101 cells. Previous studies suggested that AP-1 activity is required for maintaining the transformed phenotype in RT101 cells. Thus, Pdcd4 suppresses tumor phenotype by inhibiting AP-1-dependent transcription, possibly through inhibiting c-Jun and c-Fos activation.

Integrity signals

Registry

Crossref · 10.1038/sj.onc.1206433

Cites

37 of 37 references verified0 citation errors · 0 not checkable

Statistics

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

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Yang, H.-S., Knies, J. L., Stark, C., & Colburn, N. H.
Affiliations
National Cancer Institute (US)
Corresponding author
Yang, Hsin-Sheng
Venue
Oncogene
Published
2003-06-11
Volume
22
Issue
24
Pages
3712-3720
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
OpenAlex
W1998639716
Cited by
160
References
37
Citations by year
2025: 2 · 2024: 6 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 9 · 2015: 7 · 2014: 9 · 2013: 21 · 2012: 9
FWCI
2.63
Type
journal article
Language
en
Open access
closed
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
PDCD4, AP-1 transcription factor, c-Jun, c-fos, tumor suppressor, anchorage-independent growth, serum response element, transcriptional repression, epidermal cells
MeSH terms
Animals, Cell Division, Cell Transformation, Neoplastic, Cells, Cultured, Proteins, Transcriptional Activation, Down-Regulation, RNA-Binding Proteins, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-fos, Transcription Factor AP-1, Response Elements, Apoptosis Regulatory Proteins, 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