Evidence map›Paper›PMID 18591932›Full record

ArticleOncogene2008

HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion.

H Korkaya, A Paulson, F Iovino, M S Wicha

Open access · bronzeAbstract 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 301 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
301citing papers in PubMed, 1 pooled it
24.3field-weighted citation impact, top 1% 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

301 citing papers in PubMed, 1 synthesis or guideline pooled it, 552 citations in OpenAlex.

  1. Pooled it
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  7. Review
  8. PI3 K/AKT/mTOR pathway and its role in breast cancer stem cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025
    Review
  9. Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells.International journal of molecular sciences · 2025
    Review
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  16. Article
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  20. Article

241 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

4 authors at 1 institution in 2 countries.

H KorkayaDepartment of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. hkorkaya@med.umich.edu
A Paulson
F Iovino
M S Wicha
University of Michigan–Ann Arbor · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
Regulation of Breast Stem Cells by the MicroenvironmentR01CA101860 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WICHA, MAX S. · 2004 to 2013
$2.4M
Stem Cell Self-Renewal mammary CarcinogenesisR01CA129765 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WICHA, MAX S. · 2008 to 2015
$2.4M
NCI NIH HHS 5 P30 CA46592NCI NIH HHS CA101860NCI NIH HHS CA129765NCI NIH HHS R01 CA101860NCI NIH HHS R01 CA129765
6 · The paper itself

Abstract

The cancer stem cell hypothesis proposes that cancers arise in stem/progenitor cells through disregulation of self-renewal pathways generating tumors, which are driven by a component of 'tumor-initiating cells' retaining stem cell properties. The HER2 gene is amplified in 20-30% of human breast cancers and has been implicated in mammary tumorigenesis as well as in mediating aggressive tumor growth and metastasis. We demonstrate that HER2 overexpression drives mammary carcinogenesis, tumor growth and invasion through its effects on normal and malignant mammary stem cells. HER2 overexpression in normal mammary epithelial cells (NMEC) increases the proportion of stem/progenitor cells as demonstrated by in vitro mammosphere assays and the expression of stem cell marker aldehyde dehydrogenase (ALDH) as well as by generation of hyperplastic lesions in humanized fat pads of NOD (nucleotide-binding oligomerization domain)/SCID (severe combined immunodeficient) mice. Overexpression of HER2 in a series of breast carcinoma cell lines increases the ALDH-expressing 'cancer stem cell' population which displays increased expression of stem cell regulatory genes, increased invasion in vitro and increased tumorigenesis in NOD/SCID mice. The effects of HER2 overexpression on breast cancer stem cells are blocked by trastuzumab in sensitive, but not resistant, cell lines, an effect mediated by the PI3-kinase/Akt pathway. These studies provide support for the cancer stem cell hypothesis by suggesting that the effects of HER2 amplification on carcinogenesis, tumorigenesis and invasion may be due to its effects on normal and malignant mammary stem/progenitor cells. Furthermore, the clinical efficacy of trastuzumab may relate to its ability to target the cancer stem cell population in HER2-amplified tumors.

Indexed as

Aldehyde DehydrogenaseAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBreastBreast NeoplasmsCell Line, TumorCell ProliferationErb-b2 Receptor Tyrosine KinasesFemaleHumansMiceMice, Inbred NODMice, SCIDNeoplasm InvasivenessNeoplastic Stem CellsAldehyde DehydrogenaseAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktTrastuzumab

Identifiers

PMID18591932
PMCPMC2602947
OpenAlexW1976203623

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.