Evidence map›Paper›PMID 27753529›Full record

ArticleCell cycle (Georgetown, Tex.)2016

Cyclin G2 promotes cell cycle arrest in breast cancer cells responding to fulvestrant and metformin and correlates with patient survival.

Maike Zimmermann, Aruni P S Arachchige-Don, Michaela S Donaldson, Tommaso Patriarchi, Mary C Horne

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

Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.7field-weighted citation impact, top 13% 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

32 citing papers in PubMed, 38 citations in OpenAlex.

  1. Trial
  2. p53 and p21 Status Influences Cellular Response to Metformin inCurrent issues in molecular biology · 2026
    Article
  3. Review
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  8. Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024
    Review
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  12. Article
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  15. Article
  16. Article
  17. Article
  18. Review
  19. Cyclin-dependent kinases and rare developmental disorders.Orphanet journal of rare diseases · 2020
    Review
  20. 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 at 2 institutions in 1 country.

Maike Zimmermanna Department of Pharmacology , University of California , Davis , CA , USA.
Aruni P S Arachchige-Donb Department of Pharmacology , University of Iowa , Iowa City , IA , USA.
Michaela S Donaldsona Department of Pharmacology , University of California , Davis , CA , USA.
Tommaso Patriarchia Department of Pharmacology , University of California , Davis , CA , USA.
Mary C Hornea Department of Pharmacology , University of California , Davis , CA , USA.
University of California, Davis · USUniversity of Iowa · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Definition of cell cycle control proteins that modify tumor cell resistance to estrogen (E2) signaling antagonists could inform clinical choice for estrogen receptor positive (ER+) breast cancer (BC) therapy. Cyclin G2 (CycG2) is upregulated during cell cycle arrest responses to cellular stresses and growth inhibitory signals and its gene, CCNG2, is directly repressed by E2-bound ER complexes. Our previous studies showed that blockade of HER2, PI3K and mTOR signaling upregulates CycG2 expression in HER2+ BC cells, and that CycG2 overexpression induces cell cycle arrest. Moreover, insulin and insulin-like growth factor-1 (IGF-1) receptor signaling strongly represses CycG2. Here we show that blockade of ER-signaling in MCF7 and T47D BC cell lines enhances the expression and nuclear localization of CycG2. Knockdown of CycG2 attenuated the cell cycle arrest response of E2-depleted and fulvestrant treated MCF7 cells. These muted responses were accompanied by sustained inhibitory phosphorylation of retinoblastoma (RB) protein, expression of cyclin D1, phospho-activation of ERK1/2 and MEK1/2 and expression of cRaf. Our work indicates that CycG2 can form complexes with CDK10, a CDK linked to modulation of RAF/MEK/MAPK signaling and tamoxifen resistance. We determined that metformin upregulates CycG2 and potentiates fulvestrant-induced CycG2 expression and cell cycle arrest. CycG2 knockdown blunts the enhanced anti-proliferative effect of metformin on fulvestrant treated cells. Meta-analysis of BC tumor microarrays indicates that CCNG2 expression is low in aggressive, poor-prognosis BC and that high CCNG2 expression correlates with longer periods of patient survival. Together these findings indicate that CycG2 contributes to signaling networks that limit BC.

Indexed as

Breast NeoplasmsCell Cycle CheckpointsCell Line, TumorCell NucleusCyclin-Dependent KinasesCyclin G2Disease-Free SurvivalEstradiolEstrogensExtracellular Signal-Regulated MAP KinasesFemaleFulvestrantGene Knockdown TechniquesHumansMetforminMitogen-Activated Protein Kinase KinasesCDK10 protein, humanCyclin-Dependent KinasesCyclin G2EstradiolEstrogensExtracellular Signal-Regulated MAP KinasesFulvestrantMetforminMitogen-Activated Protein Kinase KinasesProto-Oncogene Proteins c-rafReceptors, EstrogenRetinoblastoma ProteinCCNG2CDK10Cell Cycle ArrestEstrogen DeprivationFulvestrantIGF-1RInsulinMetforminRAF/MEK/MAPK pathwayTamoxifen-Resistant

Identifiers

PMID27753529
PMCPMC5176157
OpenAlexW2535123971

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.