Evidence map›Paper›PMID 27467582›Full record

ArticleThe Journal of biological chemistry2016

Hsp90 and PKM2 Drive the Expression of Aromatase in Li-Fraumeni Syndrome Breast Adipose Stromal Cells.

Kotha Subbaramaiah, Kristy A Brown, Heba Zahid, Gabriel Balmus, Robert S Weiss, Brittney-Shea Herbert, Andrew J Dannenberg

RetractedOpen access · hybridAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Prostaglandin EThe Journal of biological chemistry · 2019
    Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Kotha SubbaramaiahFrom the Department of Medicine, Weill Cornell Medical College, New York, New York 10065, ksubba@med.cornell.edu.
Kristy A Brownthe Metabolism and Cancer Laboratory, Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia, Monash University, Clayton, Victoria 3800, Australia.
Heba Zahidthe Metabolism and Cancer Laboratory, Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia, Monash University, Clayton, Victoria 3800, Australia, the Faculty of Applied Medical Science, Taibah University, Medina, Saudi Arabia.
Gabriel Balmusthe Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, and.
Robert S Weissthe Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, and.
Brittney-Shea Herbertthe Department of Medical and Molecular Genetics, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Andrew J DannenbergFrom the Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
Cornell University · USMonash University · AUIndiana University School of Medicine

Funding

Genome maintenance by the mouse Hus1 checkpoint geneR01CA108773 · NCI · CORNELL UNIVERSITY ITHACA · PI WEISS, ROBERT S · 2004 to 2013
$2.5M
NCI NIH HHS R01 CA108773
6 · The paper itself

Abstract

Li-Fraumeni syndrome (LFS) patients harbor germ line mutations in the TP53 gene and are at increased risk of hormone receptor-positive breast cancers. Recently, elevated levels of aromatase, the rate-limiting enzyme for estrogen biosynthesis, were found in the breast tissue of LFS patients. Although p53 down-regulates aromatase expression, the underlying mechanisms are incompletely understood. In the present study, we found that LFS stromal cells expressed higher levels of Hsp90 ATPase activity and aromatase compared with wild-type stromal cells. Inhibition of Hsp90 ATPase suppressed aromatase expression. Silencing Aha1 (activator of Hsp90 ATPase 1), a co-chaperone of Hsp90 required for its ATPase activity, led to both inhibition of Hsp90 ATPase activity and reduced aromatase expression. In comparison with wild-type stromal cells, increased levels of the Hsp90 client proteins, HIF-1α, and PKM2 were found in LFS stromal cells. A complex comprised of HIF-1α and PKM2 was recruited to the aromatase promoter II in LFS stromal cells. Silencing either HIF-1α or PKM2 suppressed aromatase expression in LFS stromal cells. CP-31398, a p53 rescue compound, suppressed levels of Aha1, Hsp90 ATPase activity, levels of PKM2 and HIF-1α, and aromatase expression in LFS stromal cells. Consistent with these in vitro findings, levels of Hsp90 ATPase activity, Aha1, HIF-1α, PKM2, and aromatase were increased in the mammary glands of p53 null versus wild-type mice. PKM2 and HIF-1α were shown to co-localize in the nucleus of stromal cells of LFS breast tissue. Taken together, our results show that the Aha1-Hsp90-PKM2/HIF-1α axis mediates the induction of aromatase in LFS.

Indexed as

Gene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticAdipose TissueAnimalsAromataseBreastCarrier ProteinsCell LineFemaleHSP90 Heat-Shock ProteinsHumansLi-Fraumeni SyndromeMammary Glands, AnimalMembrane ProteinsMiceMice, KnockoutAHSA1 protein, humanAhsa1 protein, mouseAromataseCarrier ProteinsCYP19A1 protein, humanHSP90 Heat-Shock ProteinsMembrane ProteinsMolecular ChaperonesNeoplasm ProteinsThyroid Hormone-Binding ProteinsThyroid Hormonesheat shock protein 90 (Hsp90)hypoxia-inducible factor (HIF)p53pyruvate kinasesignal transduction

Identifiers

PMID27467582
PMCPMC4965552
OpenAlexW2418523864

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.