Evidence map›Paper›PMID 25111005›Full record

ArticleThe Prostate2014

RAD9 enhances radioresistance of human prostate cancer cells through regulation of ITGB1 protein levels.

Constantinos G Broustas, Howard B Lieberman

Open access · greenAbstract read
In one paragraph

Article in The Prostate, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
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  6. Review
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  9. Review
  10. Knockdown of Rad9A enhanced DNA damage induced by trichostatin A in esophageal cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  11. 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

2 authors at 1 institution in 1 country.

Constantinos G BroustasCenter for Radiological Research, Columbia University College of Physicians and Surgeons, New York, New York.
Howard B Lieberman
Columbia University · US

Funding

THE FUNCTIONAL GENOMICS OF BYSTANDER RESPONSESP01CA049062 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI HEI, TOM K. · 1990 to 2014
$21.9M
Mechanisms of Radioresistance and Cell Cycle ProgressionR01CA130536 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LIEBERMAN, HOWARD B. · 2007 to 2016
$3.5M
The MRAD9 Radioresistance GeneR01GM079107 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LIEBERMAN, HOWARD B. · 2006 to 2013
$2.6M
NCI NIH HHS P01 CA049062NCI NIH HHS P01CA49062NCI NIH HHS R01 CA130536NCI NIH HHS R01CA130536NIGMS NIH HHS R01 GM079107NIGMS NIH HHS R01GM079107
6 · The paper itself

Abstract

backgroundMouse embryonic stem cells null for Rad9 are sensitive to deleterious effects of ionizing radiation exposure. Likewise, integrin β1 is a known radioprotective factor. Previously, we showed that RAD9 downregulation in human prostate cancer cells reduces integrin β1 protein levels and ectopic expression of Mrad9 restores inherent high levels.

methodsWe used RNA interference to knockdown Rad9 expression in PC3 and DU145 prostate cancer cells. These cells were then exposed to ionizing radiation, and integrin β1 protein levels were measured by immunoblotting. Survival of irradiated cells was measured by clonogenicity, cell cycle analysis, PARP-1 cleavage, and trypan blue exclusion.

resultsThe function of RAD9 in controlling integrin β1 expression is unique and not shared by the other members of the 9-1-1 complex, HUS1 and RAD1. RAD9 or integrin β1 silencing sensitizes DU145 and PC3 cells to ionizing radiation. Irradiation of DU145 cells with low levels of RAD9 induces cleavage of PARP-1 protein. High levels of ionizing radiation have no effect on integrin β1 protein levels. However, when RAD9 downregulation is combined with 10 Gy of ionizing radiation in DU145 or PC3 cells, there is an additional 50% downregulation of integrin β1 compared with levels in unirradiated RAD9 knockdown cells. Finally, PC3 cells growing on fibronectin display increased radioresistance. However, PC3 cells with RAD9 knockdown are no longer protected by fibronectin after treatment with ionizing radiation.

conclusionsDownregulation of RAD9 when combined with ionizing radiation results in reduction of ITGB1 protein levels in prostate cancer cells, and increased lethality.

Indexed as

Cell Cycle ProteinsCell DeathCell Line, TumorDown-RegulationExonucleasesFibronectinsGene Knockdown TechniquesHumansIntegrin beta1MalePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesProstatic NeoplasmsRadiation ToleranceCell Cycle ProteinsExonucleasesFibronectinsHUS1 protein, humanIntegrin beta1PARP1 protein, humanPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesRad1 protein, humanrad9 proteinintegrin β1ionizing radiationprostate cancerRAD9

Identifiers

PMID25111005
PMCPMC4142073
OpenAlexW1582246941

What OpenQuestion holds

Textmetadata
LicenceTDM
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.