Evidence map›Paper›PMID 11585919›Full record

ArticleMolecular and cellular biology2001

claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor, encodes lung- and stomach-specific isoforms through alternative splicing.

T Niimi, K Nagashima, J M Ward, P Minoo, D B Zimonjic, N C Popescu, S Kimura

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06767449 (Multi-center Cohort Study to Evaluate the Real-world Efficacy and Safety of Zolbetuximab Plus Chemotherapy in Claudin18.2 Positive, HER2 Negative, Advanced Gastric Cancer), which is not on this map. Cited by 162 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
162citing papers in PubMed, 3 pooled it
4.0field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06767449 recruitingnot on this mapstarted 2024, after this paper: background citation

Multi-center Cohort Study to Evaluate the Real-world Efficacy and Safety of Zolbetuximab Plus Chemotherapy in Claudin18.2 Positive, HER2 Negative, Advanced Gastric Cancer

Typeobservational_patient_registrySponsorYonsei UniversityRan2024 to 2026Enrolled80ConditionsAdvanced Gastric Cancer
3 · Its place in the literature

Who cites it

162 citing papers in PubMed, 3 syntheses or guidelines pooled it, 281 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Review
  7. Review
  8. Article
  9. Claudin 18.2 Targeting: A Pan-Cancer Perspective.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Review
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  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
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  18. Article
  19. Review
  20. Review

102 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 3 countries.

T NiimiLaboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
K Nagashima
J M Ward
P Minoo
D B Zimonjic
N C Popescu
S Kimura
National Institutes of Health · USChildren's Hospital of Los Angeles · USFrederick National Laboratory for Cancer Research · USScience Applications International Corporation (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

T/EBP/NKX2.1, a member of the NKX family of homeodomain-containing transcription factors, regulates the expression of a number of genes in lung and thyroid. Here we describe the isolation and characterization of a novel target gene, termed claudin-18, that is down-regulated in the lungs of T/ebp/Nkx2.1-null mouse embryos. The gene product exhibits an amino acid sequence similar to those of the claudin multigene family of proteins that constitute tight junction strands in epithelial cells. The gene was localized by fluorescence in situ hybridization to mouse chromosome 9 at region 9E3-F1 and to human chromosome 3 at region 3q21-23. The claudin-18 gene has two promoters, each with its own unique exon 1 that is spliced to common exons 2 through 5. Alternative usage of these promoters leads to production of lung and stomach-specific transcripts. The downstream lung-specific promoter contains two T/EBP/NKX2.1 binding sites responsible for trans activation of the gene by T/EBP/NKX2.1 in lung cells. Only claudin-18 was down-regulated in T/ebp/Nkx2.1-null embryo lungs among 11 claudin transcripts examined. Furthermore, the claudin-18 transcript has an alternative 12-bp insertion derived from the 5' end of intron 4, which produces a C-terminally truncated isoform in lung and stomach. Immunohistochemistry demonstrated complete membrane localization of claudin-18 with small focal dots in the lung and stomach epithelial cells. Immunogold electron microscopy analysis revealed that claudin-18 is concentrated at the cell-cell borders of epithelial cells. These unique features suggest a potentially important role for claudin-18 in the structure and function of tight junctions in lung and stomach.

Indexed as

Alternative SplicingAmino Acid SequenceAnimalsBase SequenceBinding SitesBlotting, NorthernCell NucleusChromosome MappingChromosomesChromosomes, Human, Pair 3ClaudinsCloning, MolecularDNA, ComplementaryDown-RegulationExonsGastric MucosaClaudinsCLDN18 protein, humanCldn18 protein, mouseDNA, ComplementaryHomeodomain ProteinsLuciferasesMembrane ProteinsProtein IsoformsTranscription Factors

Identifiers

PMID11585919
PMCPMC99911
OpenAlexW2157473448

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.