Evidence map›Paper›PMID 26310443›Full record

ArticleMolecular biology of the cell2015

Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin tumorigenesis.

Jill Goldstein, Eve Roth, Natalie Roberts, Rachel Zwick, Samantha Lin, Sean Fletcher, Ana Tadeu, Christine Wu, Amanda Beck, Caroline Zeiss and 2 more

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 27% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
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  4. Review
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  8. Experimental biology and medicine (Maywood, N.J.) · 2020
    Article
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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

12 authors at 1 institution in 1 country.

Jill GoldsteinDepartment of Molecular, Cell and Developmental Biology, Yale University, New Haven, CT 06520.
Eve RothDepartment of Molecular, Cell and Developmental Biology, Yale University, New Haven, CT 06520.
Natalie RobertsDepartment of Molecular, Cell and Developmental Biology, Yale University, New Haven, CT 06520.
Rachel ZwickDepartment of Molecular, Cell and Developmental Biology, Yale University, New Haven, CT 06520.
Samantha LinDepartment of Molecular, Cell and Developmental Biology, Yale University, New Haven, CT 06520.
Sean FletcherDepartment of Molecular, Cell and Developmental Biology, Yale University, New Haven, CT 06520.
Ana TadeuDepartment of Molecular, Cell and Developmental Biology, Yale University, New Haven, CT 06520.
Christine WuDepartment of Molecular, Cell and Developmental Biology, Yale University, New Haven, CT 06520.
Amanda BeckDepartment of Comparative Medicine, Yale University, New Haven, CT 06520.
Caroline ZeissDepartment of Comparative Medicine, Yale University, New Haven, CT 06520.
Mayte Suárez-FariñasDepartments of Population Health Science and Policy, Genetics and Genomics Science, and Dermatology, Icahn School of Medicine, New York, NY 10029.
Valerie HorsleyDepartment of Molecular, Cell and Developmental Biology, Yale University, New Haven, CT 06520 Department of Dermatology, Yale University, New Haven, CT 06520 valerie.horsley@yale.edu.
Yale University · US

Funding

Training in Genomics and Proteomics TechnologiesT32HG003198 · NHGRI · YALE UNIVERSITY · PI BREAKER, RONALD R · 2004 to 2015
$4.9M
Extrinsic Regulation of Epidermal HomeostatasisR01AR060295 · NIAMS · YALE UNIVERSITY · PI HORSLEY, VALERIE · 2011 to 2016
$2.2M
Extrinsic Regulation that Regulate Skin HomeostasisR56AR060295 · NIAMS · YALE UNIVERSITY · PI HORSLEY, VALERIE · 2018 to 2018
$481k
NHGRI NIH HHS 5T32HG 3198-7NHGRI NIH HHS T32 HG003198NIAMS NIH HHS AR060295NIAMS NIH HHS R01 AR060295NIAMS NIH HHS R56 AR060295
6 · The paper itself

Abstract

Immunosuppressive therapies using calcineurin inhibitors, such as cyclosporine A, are associated with a higher incidence of squamous cell carcinoma formation in mice and humans. Calcineurin is believed to suppress tumorigenesis in part through Nfatc1, a transcription factor expressed primarily in hair follicle bulge stem cells in mice. However, mice overexpressing a constitutively active Nfatc1 isoform in the skin epithelium developed increased spontaneous skin squamous cell carcinomas. Because follicular stem cells can contribute to skin tumorigenesis, whether the endogenous expression of Nfatc1 inhibits or enhances skin tumorigenesis is unclear. Here we show that loss of the endogenous expression of Nfatc1 suppresses the rate of DMBA/TPA-induced skin tumorigenesis. Inducible deletion of Nfatc1 in follicular stem cells before tumor initiation significantly reduces the rate of tumorigenesis and the contribution of follicular stem cells to skin tumors. We find that skin tumors from mice lacking Nfatc1 display reduced Hras codon 61 mutations. Furthermore, Nfatc1 enhances the expression of genes involved in DMBA metabolism and increases DMBA-induced DNA damage in keratinocytes. Together these data implicate Nfatc1 in the regulation of skin stem cell-initiated tumorigenesis via the regulation of DMBA metabolism.

Indexed as

9,10-Dimethyl-1,2-benzanthraceneAnimalsCarcinogenesisCarcinogensCytochrome P-450 CYP2E1DNA DamageHair FollicleKeratinocytesMiceMice, KnockoutNFATC Transcription FactorsPapillomaSkinSkin NeoplasmsStem CellsTetradecanoylphorbol Acetate9,10-Dimethyl-1,2-benzanthraceneCarcinogensCytochrome P-450 CYP2E1Nfatc1 protein, mouseNFATC Transcription FactorsTetradecanoylphorbol Acetate

Identifiers

PMID26310443
PMCPMC4603931
OpenAlexW2226676383

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.