Evidence map›Paper›PMID 12592382›Full record

ArticleOncogene2003

ERK signaling pathway is involved in p15INK4b/p16INK4a expression and HepG2 growth inhibition triggered by TPA and Saikosaponin a.

Wu Wen-Sheng

Abstract readComparative Study
PubMed Publisher
In one paragraph

Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

25 citing papers in PubMed, 76 citations in OpenAlex.

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  16. TCM Formula Xiaoyaosan Decoction Improves Depressive-Like Behaviors in Rats with Type 2 Diabetes.Evidence-based complementary and alternative medicine : eCAM · 2015
    Article
  17. Current understanding on antihepatocarcinoma effects of xiao chai hu tang and its constituents.Evidence-based complementary and alternative medicine : eCAM · 2013
    Article
  18. Article
  19. 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

1 author at 1 institution in 1 country.

Wu Wen-ShengDepartment of Medical Technology, TZU CHI University, Hualien, Taiwan. wuws@mail.tcu.edu.tw
Tzu Chi University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The signal pathway mediating induction of p15(INK4b) and p16(INK4a) during HepG2 growth inhibition triggered by the phorbol ester tumor promoter TPA (12-O-tetradecanoylphorbol 13-acetate) and the Chinese herb Saikosaponin a was investigated. Western blot of three activated forms of mitogen-activated protein kinase (MAPK) (p-ERK, p-JNK and p-p38) demonstrated that phosphorylation of ERK is dramatically induced (11.6-fold ) by TPA during 15 min to 1 h and significantly induced (2.5-fold) by Saikosaponin alpha at 30 min, whereas phosphorylation of JNK was induced only by TPA during 30 min to 1 h. Phosphorylation of p38 was not induced by either drug. During this period, phosphorylation of one of the downstream transcriptional factors of MAPK cascade, ATF2, was 3.2- and 2.0-fold induced by TPA and Saikosaponin a, respectively, whereas that of another transcriptional factor, c-jun, was induced by TPA only. On the other hand, expressions of proto-oncogene c-jun, junB and c-fos were induced by TPA and Saikosaponin a during 30 min to 6 h of treatment. Pretreatment of 20 microg/ml PD98059, an inhibitor of MEK which is the upstream kinase of ERK, prevents the TPA- and Saikosaponin a-triggered HepG2 growth inhibition by 50 and 30%, respectively, accompanied by a 50 - 85% decrease of the p15(INK4b)/p16(INK4a) RNAs and proteins induced by both drugs. Inductions of c-fos RNA by both drugs and c-jun phosphorylation by TPA were also significantly reduced by PD98059 pretreatment. In addition, AP-1 DNA-binding assay using nonisotopic capillary electrophoresis and laser-induced fluorescence (CE/LIF) demonstrated that the AP-1-related DNA-binding activity was significantly induced by TPA and Saikosaponin a, which can be reduced by PD98059 pretreatment. These results suggested that activation of ERK together with its downstream transcriptional machinery mediated p15(INK4b) and p16(INK4a) expression that led to HepG2 growth inhibition.

Indexed as

Tumor Suppressor ProteinsActivating Transcription Factor 2Carcinoma, HepatocellularCell Cycle ProteinsCell DivisionCyclic AMP Response Element-Binding ProteinCyclin-Dependent Kinase Inhibitor p15Cyclin-Dependent Kinase Inhibitor p16Depression, ChemicalElectrophoresis, CapillaryEnzyme InductionEnzyme InhibitorsFlavonoidsGene Expression Regulation, NeoplasticGenes, fosGenes, jun2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-oneActivating Transcription Factor 2ATF2 protein, humanCDKN2B protein, humanCell Cycle ProteinsCyclic AMP Response Element-Binding ProteinCyclin-Dependent Kinase Inhibitor p15Cyclin-Dependent Kinase Inhibitor p16Enzyme InhibitorsFlavonoidsJNK Mitogen-Activated Protein KinasesMAP2K1 protein, humanMAP Kinase Kinase 1MAS1 protein, humanMitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesNeoplasm ProteinsOleanolic Acidp38 Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesProto-Oncogene MasProto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junsaikosaponin DSaponinsTetradecanoylphorbol AcetateTranscription Factor AP-1Transcription FactorsTumor Suppressor Proteins

Identifiers

PMID12592382
OpenAlexW1994456365

What OpenQuestion holds

Textmetadata
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.