Evidence map›Paper›PMID 18727708›Full record

ArticleClinical endocrinology2009

Down-regulation of NR4A1 in follicular thyroid carcinomas is restored following lithium treatment.

Cléber P Camacho, Flavia R M Latini, Gisele Oler, Flavio C Hojaij, Rui M B Maciel, Gregory J Riggins, Janete M Cerutti

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical endocrinology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 32% 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

7 citing papers in PubMed, 19 citations in OpenAlex.

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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

7 authors at 3 institutions in 3 countries.

Cléber P CamachoGenetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology, Federal University of São Paulo, São Paulo, Brazil.
Flavia R M Latini
Gisele Oler
Flavio C Hojaij
Rui M B Maciel
Gregory J Riggins
Janete M Cerutti
Laboratory of Molecular Genetics · PLJohns Hopkins University · USUniversidade Federal de São Paulo · BR

Funding

Preoperative and follow-up tests for thyroid tumorsR33CA113461 · NCI · JOHNS HOPKINS UNIVERSITY · PI RIGGINS, GREGORY JOSEPH · 2009 to 2010
$555k
Preoperative and follow-up tests for thyroid tumorsR21CA113461 · NCI · JOHNS HOPKINS UNIVERSITY · PI RIGGINS, GREGORY JOSEPH · 2006 to 2006
$240k
NCI NIH HHS CA113461NCI NIH HHS R21 CA113461NCI NIH HHS R33 CA113461
6 · The paper itself

Abstract

introductionThe identification of follicular thyroid adenoma-associated transcripts will lead to a better understanding of the events involved in pathogenesis and progression of follicular tumours. Using Serial Analysis of Gene Expression, we identified five genes that are absent in a malignant follicular thyroid carcinoma (FTC) library, but expressed in follicular adenoma (FTA) and normal thyroid libraries.

methodsNR4A1, one of the five genes, was validated in a set of 27 normal thyroid tissues, 10 FTAs and 14 FTCs and three thyroid carcinoma cell lines by real time PCR. NR4A1 can be transiently increased by a variety of stimuli, including lithium, which is used as adjuvant therapy of thyroid carcinoma with (131)I. We tested if lithium could restore NR4A1 expression. The expression of other genes potentially involved in the same signalling pathway was tested. To this end, lithium was used at different concentration (10 mm or 20 mm) and time (2 h and 24 h) and the level of expression was tested by quantitative PCR. We next tested if Lithium could affect cell growth and apoptosis.

resultsWe observed that NR4A1 expression was under-expressed in most of the FTCs investigated, compared with expression in normal thyroid tissues and FTAs. We also found a positive correlation between NR4A1 and FOSB gene expression. Lithium induced NR4A1 and FOSB expression, reduced CCDN1 expression, inhibited cell growth and triggered apoptosis in a FTC cell line.

conclusionsNR4A1 is under-expressed in most of FTCs. The loss of expression of both NR4A1 and the Wnt pathway gene FOSB was correlated with malignancy. This is consistent with the hypothesis that its loss of expression is part of the transformation process of FTCs, either as a direct or indirect consequence of Wnt pathway alterations. Lithium restores NR4A1 expression, induces apoptosis and reduces cell growth. These findings may explain a possible molecular mechanism of lithium's therapeutic action.

Indexed as

Adenocarcinoma, FollicularAdenomaApoptosisCell Line, TumorCell ProliferationChemotherapy, AdjuvantCyclin D1DNA-Binding ProteinsDose-Response Relationship, DrugDown-RegulationHumansLithium CompoundsNuclear Receptor Subfamily 4, Group A, Member 1Proto-Oncogene Proteins c-fosReceptors, SteroidSignal TransductionCCND1 protein, humanCyclin D1DNA-Binding ProteinsFOSB protein, humanLithium CompoundsNR4A1 protein, humanNuclear Receptor Subfamily 4, Group A, Member 1Proto-Oncogene Proteins c-fosReceptors, SteroidWnt Proteins

Identifiers

PMID18727708
PMCPMC2742303
OpenAlexW2153638958

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Registered trials

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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.