Evidence map›Paper›PMID 18332865›Full record

ArticleOncogene2008

Suppression of PTEN function increases breast cancer chemotherapeutic drug resistance while conferring sensitivity to mTOR inhibitors.

L S Steelman, P M Navolanic, M L Sokolosky, J R Taylor, B D Lehmann, W H Chappell, S L Abrams, E W T Wong, K M Stadelman, D M Terrian and 6 more

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

Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

93 citing papers in PubMed, 171 citations in OpenAlex.

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33 more citing papers are in PubMed but not listed here.

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

16 authors at 4 institutions in 3 countries.

L S SteelmanDepartment of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA.
P M Navolanic
M L Sokolosky
J R Taylor
B D Lehmann
W H Chappell
S L Abrams
E W T Wong
K M Stadelman
D M Terrian
N R Leslie
A M Martelli
F Stivala
M Libra
R A Franklin
J A McCubrey
East Carolina University · USUniversity of Catania · ITUniversity of Bologna · ITUniversity of Dundee · GB

Funding

Ras/Raf &PI3K/Akt Induced Breast Cancer Drug ResistanceR01CA098195 · NCI · EAST CAROLINA UNIVERSITY · PI MC CUBREY, JAMES A · 2003 to 2007
$1.5M
Medical Research Council G9403619NCI NIH HHS R01 CA098195NCI NIH HHS R01CA098195
6 · The paper itself

Abstract

Ectopic expression of mutant forms of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) lacking lipid (G129E) or lipid and protein (C124S) phosphatase activity decreased sensitivity of MCF-7 breast cancer cells, which have wild-type PTEN, to doxorubicin and increased sensitivity to the mammalian target of rapamycin (mTOR) inhibitor rapamycin. Cells transfected with a mutant PTEN gene lacking both lipid and protein phosphatase activities were more resistant to doxorubicin than cells transfected with the PTEN mutant lacking lipid phosphatase activity indicating that the protein phosphatase activity of PTEN was also important in controlling the sensitivity to doxorubicin, while no difference was observed between the lipid (G129E) and lipid and protein (C124S) phosphatase PTEN mutants in terms of sensitivity to rapamycin. A synergistic inhibitory interaction was observed when doxorubicin was combined with rapamycin in the phosphatase-deficient PTEN-transfected cells. Interference with the lipid phosphatase activity of PTEN was sufficient to activate Akt/mTOR/p70S6K signaling. These studies indicate that disruption of the normal activity of the PTEN phosphatase can have dramatic effects on the therapeutic sensitivity of breast cancer cells. Mutations in the key residues which control PTEN lipid and protein phosphatase may act as dominant-negative mutants to suppress endogenous PTEN and alter the sensitivity of breast cancer patients to chemo- and targeted therapies.

Indexed as

Drug Resistance, NeoplasmMutation, MissenseSignal TransductionAmino Acid SubstitutionAntibiotics, AntineoplasticBreast NeoplasmsCell Line, TumorDoxorubicinDrug SynergismFemaleGene ExpressionHumansProtein KinasesProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseRibosomal Protein S6 Kinases, 70-kDaAntibiotics, AntineoplasticDoxorubicinMTOR protein, humanProtein KinasesProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePTEN protein, humanRibosomal Protein S6 Kinases, 70-kDaSirolimusTOR Serine-Threonine Kinases

Identifiers

PMID18332865
PMCPMC3836277
OpenAlexW2076203883

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.