Evidence map›Paper›PMID 11360194›Full record

ArticleOncogene2001

Expression of a truncated 100 kDa HER2 splice variant acts as an endogenous inhibitor of tumour cell proliferation.

A Aigner, H Juhl, C Malerczyk, A Tkybusch, C C Benz, F Czubayko

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 55 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. The HER2 Signaling Network in Breast Cancer--Like a Spider in its Web.Journal of mammary gland biology and neoplasia · 2014
    Review
  11. Interference-Free HER2 ECD as a Serum Biomarker in Breast Cancer.Journal of molecular biomarkers & diagnosis · 2014
    Article
  12. Article
  13. TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. 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

6 authors at 3 institutions in 2 countries.

A AignerDepartment of Pharmacology and Toxicology, Philipps-University Marburg, Karl-von-Frisch-Strasse 1, D-35033 Marburg, Germany.
H Juhl
C Malerczyk
A Tkybusch
C C Benz
F Czubayko
Philipps University of Marburg · DEGeorgetown University · USKiel University · DE

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI STEPHEN W BYERS · 1990 to 2026
$71.5M
NCI NIH HHS 2P30-CA-51008
6 · The paper itself

Abstract

Overexpression of the HER2 (neu/c-erbB-2) oncogene frequently coincides with an aggressive clinical course of certain human adenocarcinomas. Expression and secretion of aberrant HER2 splice variants has been reported in various cell lines and tissues and can interfere with the oncogenic HER2 activity. Here we demonstrate, using two different approaches, that expression of a truncated 100 kDa HER2 variant which encodes the extracellular domain of HER2 (HER-ECD) inhibits growth factor-mediated tumour cell proliferation. A HER2-ECD cDNA encoding the truncated variant was overexpressed in MCF7 breast cancer cells. HER2-ECD overexpression decreased spontaneous proliferation of MCF7 cells as well as heregulin-mediated soft agar colony formation. Concomitantly, heregulin-induced phosphorylation of HER4 as well as downstream activation of p44/p42 MAP-kinases was decreased. To confirm these data, ribozymes were targeted to the 3'-untranslated region of the 2.3 kb HER2-ECD mRNA which is spontaneously expressed in MKN7 gastric cancer cells. HER2-ECD-targeted ribozymes downregulated HER2-ECD expression and enhanced EGF-mediated soft agar colony formation of MKN7 cells. In parallel, EGF-induced activation of p44/p42 MAP-kinases and activation of c-Fos expression were increased in ribozyme-transfected MKN7 cells. Finally, in RT-PCR we found a trend towards a progressive loss of 2.3 kb HER2-ECD mRNA expression in more advanced gastric tumours. These data show that the HER2-ECD variant inhibits growth factor-mediated tumour cell proliferation suggesting an important role during the progression of human cancer.

Indexed as

Alternative SplicingBase SequenceBreast NeoplasmsCell DivisionDNA, ComplementaryDown-RegulationDoxycyclineEpidermal Growth FactorErb-b2 Receptor Tyrosine KinasesGenes, erbB-2Growth InhibitorsHumansMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesDNA, ComplementaryDoxycyclineEpidermal Growth FactorErb-b2 Receptor Tyrosine KinasesGrowth InhibitorsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNeuregulin-1RNA, CatalyticRNA, Messenger

Identifiers

PMID11360194
OpenAlexW1967141802

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.