Context dependent roles for RB-E2F transcriptional regulation in tumor suppression.

Michael J Thwaites, Matthew J Cecchini, Daniel T Passos, Komila Zakirova, Frederick A Dick

Abstract read

In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

–field-weighted citation impact

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

1 citing paper in PubMed.

Monitoring the Cell Cycle of Tumor Cells in Mouse Models of Human Cancer.Cold Spring Harbor perspectives in medicine · 2023
Article

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

5 authors.

Michael J ThwaitesLondon Regional Cancer Program, Lawson Health Research Institute, London, Ontario, Canada.

Matthew J CecchiniDepartment of Pathology, Western University, London, Ontario, Canada.

Daniel T PassosLondon Regional Cancer Program, Lawson Health Research Institute, London, Ontario, Canada.

Komila ZakirovaLondon Regional Cancer Program, Lawson Health Research Institute, London, Ontario, Canada.

Frederick A DickLondon Regional Cancer Program, Lawson Health Research Institute, London, Ontario, Canada.ORCID 0000-0002-0047-9985

Funding

CIHR MOP-89765

6 · The paper itself

Abstract

RB-E2F transcriptional control plays a key role in regulating the timing of cell cycle progression from G1 to S-phase in response to growth factor stimulation. Despite this role, it is genetically dispensable for cell cycle exit in primary fibroblasts in response to growth arrest signals. Mice engineered to be defective for RB-E2F transcriptional control at cell cycle genes were also found to live a full lifespan with no susceptibility to cancer. Based on this background we sought to probe the vulnerabilities of RB-E2F transcriptional control defects found in Rb1R461E,K542E mutant mice (Rb1G) through genetic crosses with other mouse strains. We generated Rb1G/G mice in combination with Trp53 and Cdkn1a deficiencies, as well as in combination with KrasG12D. The Rb1G mutation enhanced Trp53 cancer susceptibility, but had no effect in combination with Cdkn1a deficiency or KrasG12D. Collectively, this study indicates that compromised RB-E2F transcriptional control is not uniformly cancer enabling, but rather has potent oncogenic effects when combined with specific vulnerabilities.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsCarcinogenesisCell CycleCells, CulturedCyclin-Dependent Kinase Inhibitor p21Disease Models, AnimalE2F Transcription FactorsFibroblastsGenetic Predisposition to DiseaseHumansKi-67 AntigenMiceMice, TransgenicMutationNeoplasmsCdkn1a protein, mouseCyclin-Dependent Kinase Inhibitor p21E2F Transcription FactorsHras protein, mouseKi-67 AntigenProto-Oncogene Proteins p21(ras)Retinoblastoma ProteinTrp53 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID30703085

DOI10.1371/journal.pone.0203577

PMCPMC6354955

What OpenQuestion holds

Textmetadata

LicenceCC BY

Read underepoch 390

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.