Evidence map›Paper›PMID 29959569›Full record

ArticleJournal of cancer research and clinical oncology2018

Disruption of MEK/ERK/c-Myc signaling radiosensitizes prostate cancer cells in vitro and in vivo.

Carmela Ciccarelli, Agnese Di Rocco, Giovanni Luca Gravina, Annunziata Mauro, Claudio Festuccia, Andrea Del Fattore, Paolo Berardinelli, Francesca De Felice, Daniela Musio, Marina Bouché and 3 more

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

Article in Journal of cancer research and clinical oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 52 citations in OpenAlex.

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  13. EnhancingJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022
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  19. Targeting treatment options for castration-resistant prostate cancer.American journal of clinical and experimental urology · 2021
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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

13 authors at 4 institutions in 1 country.

Carmela CiccarelliDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy.
Agnese Di RoccoDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy.
Giovanni Luca GravinaDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy.
Annunziata MauroUnit of Basic and Applied Biosciences, Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy.
Claudio FestucciaDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy.
Andrea Del FattoreMulti-Factorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, IRCCS, Viale di San Paolo 15, 00146, Rome, Italy.
Paolo BerardinelliUnit of Basic and Applied Biosciences, Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy.
Francesca De FeliceDivision of Radiotherapy, Department of Radiology, Radiation Oncology and Human Pathology, "Sapienza" University of Rome, Rome, Italy.
Daniela MusioDivision of Radiotherapy, Department of Radiology, Radiation Oncology and Human Pathology, "Sapienza" University of Rome, Rome, Italy.
Marina BouchéUnit of Histology, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy.
Vincenzo TomboliniUnit of Histology, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy.
Bianca Maria ZaniDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy. biancamaria.zani@univaq.it.
Francesco MaramponDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy. f.marampon@gmail.com.ORCID http://orcid.org/0000-0002-0588-3039
University of L'Aquila · ITSapienza University of Rome · ITUniversity of Teramo · ITBambino Gesù Children's Hospital · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeProstate cancer (PCa) cell radioresistance causes the failure of radiation therapy (RT) in localized or locally advanced disease. The aberrant accumulation of c-Myc oncoprotein, known to promote PCa onset and progression, may be due to the control of gene transcription and/or MEK/ERK-regulated protein stabilization. Here, we investigated the role of MEK/ERK signaling in PCa.

methodsLnCAP, 22Rv1, DU145, and PC3 PCa cell lines were used in in vitro and in vivo experiments. U0126, trametinib MEK/ERK inhibitors, and c-Myc shRNAs were used. Radiation was delivered using an x-6 MV photon linear accelerator. U0126 in vivo activity alone or in combination with irradiation was determined in murine xenografts.

resultsInhibition of MEK/ERK signaling down-regulated c-Myc protein in PCa cell lines to varying extents by affecting expression of RNA and protein, which in turn determined radiosensitization in in vitro and in vivo xenograft models of PCa cells. The crucial role played by c-Myc in the MEK/ERK pathways was demonstrated in 22Rv1 cells by the silencing of c-Myc by means of short hairpin mRNA, which yielded effects resembling the targeting of MEK/ERK signaling. The clinically approved compound trametinib used in vitro yielded the same effects as U0126 on growth and C-Myc expression. Notably, U0126 and trametinib induced a drastic down-regulation of BMX, which is known to prevent apoptosis in cancer cells.

conclusionsThe results of our study suggest that signal transduction-based therapy can, by disrupting the MEK/ERK/c-Myc axis, reduce human PCa radioresistance caused by increased c-Myc expression in vivo and in vitro and restores apoptosis signals.

Indexed as

AnimalsCell Line, TumorDown-RegulationHumansMaleMAP Kinase Signaling SystemMiceMice, NudeProstatic NeoplasmsProto-Oncogene Proteins c-mycRadiation ToleranceRNA, Small InterferingSignal TransductionXenograft Model Antitumor AssaysProto-Oncogene Proteins c-mycRNA, Small InterferingC-MycERKsProstate cancerRadioresistanceRadiotherapyU0126

Identifiers

PMID29959569
PMCPMC11813462
OpenAlexW2810651251

What OpenQuestion holds

Textmetadata
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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.